How to add to and remove from system's environment variable "PATH"?

Here's something that does what you want which is similar to code in the jaraco.windows project. And like it, only uses built-in Python modules—so doesn't require first downloading and installing the pywin32 extensions. Plus it's Python 2.6+ and 3.x compatible and supports Unicode environment variables and values (directory paths in this case).

Note that Windows administrator rights are required to change the permanent system-level environment variables.

import ctypes
from ctypes.wintypes import HWND, UINT, WPARAM, LPARAM, LPVOID
LRESULT = LPARAM  # synonymous
import os
import sys
try:
    import winreg
    unicode = str
except ImportError:
    import _winreg as winreg  # Python 2.x

class Environment(object):
    path = r'SYSTEM\CurrentControlSet\Control\Session Manager\Environment'
    hklm = winreg.ConnectRegistry(None, winreg.HKEY_LOCAL_MACHINE)
    key = winreg.OpenKey(hklm, path, 0, winreg.KEY_READ | winreg.KEY_WRITE)
    SendMessage = ctypes.windll.user32.SendMessageW
    SendMessage.argtypes = HWND, UINT, WPARAM, LPVOID
    SendMessage.restype = LRESULT
    HWND_BROADCAST = 0xFFFF
    WM_SETTINGCHANGE = 0x1A
    NO_DEFAULT_PROVIDED = object()

    def get(self, name, default=NO_DEFAULT_PROVIDED):
        try:
            value = winreg.QueryValueEx(self.key, name)[0]
        except WindowsError:
            if default is self.NO_DEFAULT_PROVIDED:
                raise ValueError("No such registry key", name)
            value = default
        return value

    def set(self, name, value):
        if value:
            winreg.SetValueEx(self.key, name, 0, winreg.REG_EXPAND_SZ, value)
        else:
            winreg.DeleteValue(self.key, name)
        self.notify()

    def notify(self):
        self.SendMessage(self.HWND_BROADCAST, self.WM_SETTINGCHANGE, 0, u'Environment')

Environment = Environment()  # singletion - create instance

PATH_VAR = 'PATH'

def append_path_envvar(addpath):
    def canonical(path):
        path = unicode(path.upper().rstrip(os.sep))
        return winreg.ExpandEnvironmentStrings(path)  # Requires Python 2.6+
    canpath = canonical(addpath)
    curpath = Environment.get(PATH_VAR, '')
    if not any(canpath == subpath
                for subpath in canonical(curpath).split(os.pathsep)):
        Environment.set(PATH_VAR, os.pathsep.join((curpath, addpath)))

def remove_envvar_path(folder):
    """ Remove *all* paths in PATH_VAR that contain the folder path. """
    curpath = Environment.get(PATH_VAR, '')
    folder = folder.upper()
    keepers = [subpath for subpath in curpath.split(os.pathsep)
                if folder not in subpath.upper()]
    Environment.set(PATH_VAR, os.pathsep.join(keepers))

Sample usage:

print(Environment.get('path'))
append_path_envvar(r'C:\path\to\myprogram\dist')
append_path_envvar(r'D:\another\path\to\myprogram\dist')
print(Environment.get('path'))
remove_envvar_path(r'\myprogram')  # remove *both* added paths
print(Environment.get('path'))

import _winreg as reg
import win32gui
import win32con


# read the value
key = reg.OpenKey(reg.HKEY_CURRENT_USER, 'Environment', 0, reg.KEY_ALL_ACCESS)
# use this if you need to modify the system variable and if you have admin privileges
#key = reg.OpenKey(reg.HKEY_LOCAL_MACHINE, r'SYSTEM\CurrentControlSet\Control\Session Manager\Environment', 0, reg.KEY_ALL_ACCESS) 
try
    value, _ = reg.QueryValueEx(key, 'PATH')
except WindowsError:
    # in case the PATH variable is undefined
    value = ''

# modify it
value = ';'.join([s for s in value.split(';') if not r'\myprogram' in s])

# write it back
reg.SetValueEx(key, 'PATH', 0, reg.REG_EXPAND_SZ, value)
reg.CloseKey(key)

# notify the system about the changes
win32gui.SendMessage(win32con.HWND_BROADCAST, win32con.WM_SETTINGCHANGE, 0, 'Environment')