A randomized double-blind trial was conducted to assess the efficacy of a twice-a-week application of 1% niclosamide lotion for prevention of Schistosoma haematobium reinfection. Six hundred farmers in Fayoum, Egypt, 18–40 years of age, were treated to cure their S. haematobium infection, then randomly assigned to self-apply niclosamide or placebo lotion to their limbs, neck, and torso. Subjects were exposed to schistosomal-infested water during routine irrigation activities from April to October 1992. Three hundred fifty subjects met the inclusion criteria and completed the trial, 169 (48.3%) in the niclosamide group and 181 (51.7%) in the placebo group. The subjects assigned to the niclosamide-treated group were comparable with those in the placebo group in age (27.2 versus 27.8 years), total water contact (101.9 versus 109.9 hr), lotion application compliance (93.5% versus 90.6%), and avoidance of whole body water contact (94.7% versus 96.7%). The reinfection rate with S. haematobium was 30.8% in the niclosamide-treated group and 28.2% in the placebo group. Niclosamide lotion applied to the limbs and trunk twice a week failed to prevent S. haematobium reinfection.