[I haven't logged in for a tenday or so. Apolgies for the late response.]

In an earlier post, Anonymous Monk wrote:

"The approach suggested by kcott (compiling the combined regex; not the tie stuff) should be fairly efficient."

I'd just like to say that I concur with the "not the tie stuff" part.

"... to address some of the questions in kcott's reply ..."

Thanks for that. I think you shouldn't use any modules at all (except the pragmata). Consider code like this:

#!/usr/bin/env perl
#
#   pm_1155868_first_grep_large_file_2.pl [no modules]
#

use strict;
use warnings;
use autodie;

open my $lines_fh, '<', input_filename();
while (<$lines_fh>) {
    next unless is_a_match($_);
    process_match($_) and last;
}

sub input_filename { 'pm_1155868_input.txt' }
sub get_strings { [qw{rst uvw xyz}] }
BEGIN {
    my $re = '(?:' . join('|', @{get_strings()}) . ')';
    sub is_a_match { $_[0] =~ /$re/ }
}
sub process_match { print "Match: $_[0]" }
[download]

It produces the same output:

$ pm_1155868_first_grep_large_file_2.pl
Match: dddddddxyzdddd
[download]

• You'll need to modify &input_filename, &get_strings and &process_match to suit.
• $re and &is_a_match should work fine as is; modify if necessary.
• Note how the while loop ignores all records that don't match (next); when the first match is found, it uses it and then exits the loop (last). This seems to match your requirements.
• Use Benchmark, as previously discussed, to compare potential solutions.