The rate of head louse infestations is increasing. Most of the neurotoxic treatments are not reliably ovicidal and are faced with genetic resistance. The treatments based on a mechanical mode of action show no sufficient efficacy, transferring the chances of a cure on a tedious combing or leaving the hair fatty. This double-blinded, randomized, controlled, superiority trial evaluates the efficacy and safety of a novel mixture made of semi-crystalline polymers and plant extracts. Forty-five participants received a single application of either 1% Permethrin lotion or the novel lotion, applied for 15 minutes. Untreated and treated nits were collected and placed in an incubator during 10 days. The worst case intent-to-treat analysis found the novel lotion significantly more effective than 1% Permethrin, with 21/22 (95.5%) participants cured and 9/23 (39.1%), respectively (p < 0.0001). Rate of viable nymphs was 0.5 (2.1) for the new lotion and 40.8 (20.4) for the 1% Permethrin. The new lotion cures head louse infestations, offering an effective alternative treatment, with a high efficacy for inhibiting the hatching of eggs. Its physical actions on lice and their eggs should not be affected by resistance to neurotoxic insecticides