Install the plugin
Open Plugins › Plugins Admin, tick ComparePlus (the maintained successor of the old Compare plugin), click Install and let Notepad++ restart. On 64-bit Windows make sure you are running the 64-bit Notepad++; plugins must match the architecture.
Compare two open files
Open both files in tabs. With the second file active, press Ctrl+Alt+C (Plugins › ComparePlus › Compare); the old Compare plugin used Alt+D. The two tabs are placed side by side: added lines in green, removed in red, changed in orange with the differing characters highlighted, and a grey placeholder where one side has nothing.
Ctrl+Alt+C Compare the two most recent tabs Ctrl+Alt+X Clear the active comparison Ctrl+Alt+PgDn / PgUp Next / previous difference Ctrl+Alt+Home / End First / last difference
Useful options
ComparePlus › Settings lets you ignore spaces, ignore case, ignore empty lines and detect moved blocks so a reordered function is not shown as a delete plus an add. Compare to last save diffs the current buffer against the file on disk, which is a fast check before you overwrite something.
When Notepad++ is not the right tool
For folders, use WinMerge. For files in a Git repository, git diff or VS Code shows history as well. For text that is not saved anywhere, or on a machine without Notepad++, paste both versions into the online diff checker.
FAQ
Why is the Compare plugin missing from Plugins Admin?
The original Compare plugin was replaced by ComparePlus. Search for ComparePlus; if Plugins Admin is empty, your Notepad++ was installed without it, so download the plugin release and drop the folder into plugins manually.
Can Notepad++ compare two folders?
No. Use WinMerge or, from a command prompt, robocopy src dst /L /E to list differences.