Abstract: One hundred seventy-two subjects with head lice participated in a five-way, investigator-blinded, parallel-group, active-controlled study comparing 0.5% malathion gel (30, 60, and 90 minutes applications), Ovide® Lotion (0.5% malathion), and Nix® Crème Rinse (1% permethrin). All subjects were treated on day 1. Participants were reevaluated at day 8 ± 1 and those with live lice were retreated with the same product, for the same duration as day 1. Cure, defined as the absence of live lice, was evaluated 14 ± 2 days after the last treatment and 161 subjects completed the study according to the protocol. Compared to Nix, treatment success rates were statistically superior for all malathion gel and Ovide® groups. Retreatment rate for Nix was 70%, which was statistically more than the malathion groups. The highest treatment success rates were observed for the 30-minute malathion gel (98% intent-to-treat and 100% per-protocol [PP]) and the 8 to 12 hour Ovide® application (97% intent-to-treat and 100% PP). In conclusion, the 30-minute malathion gel, which contains the same ingredients and concentrations as Ovide®, provides comparable efficacy, offers increased safety and is more cosmetically acceptable than Ovide®.