I think you meant

local $/;
my $file = <IN>;
while( $file=~/$regex/gm ) { ... }
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There are three differences:

• The first snippet reads the file a line at a time, whereas the above snippet reads the whole file at once. The latter uses more memory, but it might be a bit faster. In practice, this difference isn't usually noticeable.

• The first snippet will only find matches that occur within the span of one line, whereas the above snippet might find matches that span multiple lines.

• Using the first snippet, you can group matches by line. You cannot do so with the above snippet.

Update: Added third difference.