Yes, doing the prepare once will increase performance quite a bit.
Another thing that can make a HUGE difference in performance is running all of the updates (or insertions) as a single transaction. From one of my DB creation programs (million records). I like to make the "work" as a sub framed by BEGIN and COMMIT to make the transaction scope clear: 
$dbh->do("BEGIN");  #a single transaction makes this MUCH faster
import_data();
$dbh->do("COMMIT");

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In reply to Re^4: Perl DBI to MySQL LOAD_FILE by Marshall
in thread Perl DBI to MySQL LOAD_FILE by Hammer2001

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