We conducted a study to determine if soap containing 1.2% triclocarban would be effective in reducing the incidence of impetigo. We randomized 162 households in a low-income neighborhood of Karachi, Pakistan, to receive a regular supply of 1.2% triclocarban-containing soap (n = 81) or an identically appearing placebo (n = 81); 79 households in a nearby neighborhood were enrolled as standard practice controls. After adjustment for household clustering and covariates, the incidence of impetigo among children living in households receiving triclocarban-containing soap (1.10 episodes per 100 person-weeks) was 23% lower than in households receiving placebo soap (P = 0.28) and 43% lower than the standard habit and practice controls (P = 0.02). The routine use of triclocarban-containing soap by children living in a community with a high incidence of impetigo was associated with a reduced incidence of impetigo.