how to run another instance of notepad++?

The base Notepad++ writes to the registry even when run in its built in portable mode. So our portable launcher needs to backup and restore that. Two instances are unsupported as a result.

As a workaround, you could open the Notepad++Portable.ini within Notepad++Portable\App\AppInfo\Launcher and rename the 3 notepad++.exe entries in the first section to something else and then rename the appropriate EXEs within Notepad++Portable\App\Notepad++ and Notepad++Portable\App\Notepad++64 to match. Note that this may or may not work, will need to be redone after each upgrade, and is completely unsupported.

If you Open Notepad++ and then drag a tab out of the main window, Notepad++ will create a 2nd instance.

Not tested if it causes issues with leaving registry entries.
It will keep the tabs of the last closed instance.

I solve the 'instance is already running' problem with a batch file I've written and installed as a 'parallel' portable app. This batch file starts the PA version if Npp is not running, otherwise it uses the currently active process. Note: all instances of " MUST be replaced with the regular ASCII double quote character, all instances of ' can be replaced with the regular ASCII single quote character.

@echo off
:: Npp{mas}.bat -- version 1.01b (2023.11.15^)

:: if Notepad++ is not running, start the PortableApp version
::  else use whatever version is running

:: =======================================================================

:: Note:    this code is not licensed, warranted, guaranteed or supported for any application or use

:: =======================================================================
:: limitations:
::  does NOT block launching a local Notepad++ session using the '-multiInst -nosession' flags
::    nor is it fully/properly tested with all combinations of these flags
::  developed on a Win7 Pro (x64) system
::  only tested briefly on a Win8.1 (x32) system
::  assumes 'Command Extensions' are enabled

:: =======================================================================
:: assumes this 'app' is located next (parallel) to the standard Notepad++ folder in the PortableApp directory:
:: notes:
::  the '-mas' suffix is my default for non-standard PortableApp program 'installations'
::  the '{mas *}' suffixes are used to separate this code from the PortableApp and/or Notepad++ code
::
:: D:\PortableApps\
:: |-- Notepad++-mas                    this 'app'
:: |   |-- App\
:: |   |   `-- AppInfo\
:: |   |       |-- appicon.ico          copied from the default Notepad++Portable folder
:: |   |       `-- appinfo.ini          copied from the default Notepad++Portable folder (see below)
:: |   `-- Npp{mas}.bat                 this file
:: |-- Notepad++Portable\               default PortableApp version of Notepad++
:: |   |--

:: the AppInfo file has minimal changes from the installed/default AppInfo file:
:: D:\PortableApps\Notepad++-mas\App\AppInfo\appinfo.ini
::  [Details]
::  Name=Notepad++ {mas launcher}       suffix differentiates this app from the default in the menu
::
::  [Control]
::  Start=Npp{mas}.bat                  arbitrary name, but must match this batch file name

:: =======================================================================
:: =======================================================================
:start

:: -----------------------------------------------------------------------
:checkIfRunning
:: determine if a Notepad++ session is active

:Tasklist
:: if Notepad++ is running, the Tasklist code shows:
::
::Image Name:   notepad++.exe
::PID:          ????
::Modules:      ntdll.dll
::              (other traceable DLLs)
::
::else Tasklist shows:
::INFO: No tasks are running which match the specified criteria.

::  usebackq                                protect the double quotes in the for loop argument
::  tokens=3                                1=Image  2=Name:  3=notepad++.exe  (will be assigned to %%A)
::  tasklist                                lists the running processes
::      /M                                  focus on modules
::      /FI "imagename eq notepad++.exe"    filter in  :: name must match 'notepad++.exe'
::      /FO list                            filter out :: list format (see results shown above)
::
:: note the 'inverse' logic used to detect the 'INFO: No tasks' message; the /FI flag has narrowed the search field
:: if Notepad++ is running, the 'if' compare fails and execution falls through to the ':useExisting' code
::
for /F "usebackq tokens=3" %%A in ( `tasklist /M /FI "imagename eq notepad++.exe" /FO list` ) do if /i not ["%%A"]==["notepad++.exe"] (

REM :cmdow
REM :: normally I use 'cmdow' for task detection and manipulation (a cleaner, more unix-like interface)
REM :: but using 'Tasklist' ensures other computers have all the required support files
REM :: cmdow - Ritchie Lawrence / Jason Hood
REM :: MIT License
REM :: https://github.com/adoxa/cmdow
REM :: /e checks for the process, returns ERRORLEVEL 0 if running
REM cmdow Notepad++* /e
REM if ERRORLEVEL 1 (

    rem the remaining/following code is common to both detection techniques
    if defined _VERBOSE echo starting Notepad++Portable
    start "Npp{mas}" "..\Notepad++Portable\Notepad++Portable.exe" %*
    exit /b 0  )


:: -----------------------------------------------------------------------
:useExisting
:: use the currently running version (may be the PortableApp version, may be the system installed version)
:: Note:  does not always force the window for the running task to the top of the desktop Z order
:: uses Powershell to get the full path of the running version
:: Note:  PowerShell will object if Notepad++ is not running, but the above :checkIfRunning code handled that case

:: https://superuser.com/a/984759
::  usebackq        protect the double quotes in the for loop argument
::                  the double quotes are needed to protect the ')' in the for loop argument
::  delims=         tell cmd to NOT use regular 'for' loop result parsing based on spaces or tabs
::
for /f "usebackq delims=" %%A in ( `PowerShell "(Get-Process Notepad++).Path"` ) do (
    if defined _VERBOSE echo using the existing Notepad++ process
    "%%~A" %*
    exit /b 0  )


:: -----------------------------------------------------------------------
:exit
:: failed to detect or (re)launch Notepad++ - set a non-zero ERRORLEVEL
exit /b 1

A more simple way is just add an entry in the launcher ini.

[Launch]
SingleAppInstance=false

But do not complaint 2 set of data, local and portable, mix up.