Background: Increasing in the prevalence of pediculosis among school students and upward trend of pesticide marketing with evidence of resistance to them, indicate the possibility of lice resistance. Objective: To compare 3 drug formulations including: Lindan shampoo 1%, permethrin shampoo 1% and Copex powder 0.5% in the treatment of head lice infestation. Patients and Methods: Ninety students with a confirmed diagnosis of pediculosis were selected from rural schools and randomly treated in 3 equal groups with the mentioned medications. The results were evaluated after 24 hours, 1, 2 and 6 weeks. Results: The rate of healing was 83.3%, 100%, 100% after 24 hours, 70%, 93.3%, 90% after 1 week, 63.3%, 90%, 76.7% after 2 weeks and 40%, 83.3%, 66.7% after 6 weeks in patients treated with Lindan, permethrin, and Copex powder, respectively (P<0.05, chi-square test). Conclusion: Considering the numerous side effects of current treatment options like Lindan, alternative treatments must be trailed especially in fall and winter because of high rate of infestation during these seasons to interfere with resistancy.