In a randomized, evaluator-blinded clinical trial, 190 patients were treated for Pediculus humanus capitis infestations with a pyrethrin-piperonyl-butoxide pediculicide (RID; Py-PB) and a permethrin pediculicide (NIX; PM). A total of 160 patients were evaluable for nit-combing speed, 156 patients were evaluable for efficacy at day 7, and 150 patients were evaluable for efficacy at day 14. Both Py-PB and PM showed 100% efficacy at day 7. At day 14, one patient in the PM group had an apparent reinfestation. The Py-PB group had significantly lower mean combing times (P=0.04), but because the PM group had more nits, the two groups were not significantly different in combing speed expressed as seconds per nit. Multiple regression and covariance analyses suggested that the greater speed of the Py-PB comb might have been masked by this baseline difference. Three patients had mild adverse experiences (Py-PB: erythema, PM: erythema and tingling sensation). No patients were removed from the study because of adverse events. In conclusion, this controlled clinical study demonstrated that both Py-PB and PM provided 100% efficacy following a single application. Differences attributable to comb design favored the Py-PB "rake" comb, but this requires additional evaluation and confirmation.