This randomized, double-blind, placebo-controlled trial evaluated the efficacy of hydroxychloroquine as postexposure prophylaxis for Covid-19. The study enrolled 821 asymptomatic adults who had high-risk or moderate-risk exposure to a confirmed Covid-19 case within 4 days. Participants were randomly assigned to receive either hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days) or a placebo. The primary outcome was the incidence of laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. The results showed no significant difference in the incidence of new illness compatible with Covid-19 between the hydroxychloroquine group (11.8%) and the placebo group (14.3%), with an absolute difference of −2.4 percentage points (P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. The study concluded that hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.This randomized, double-blind, placebo-controlled trial evaluated the efficacy of hydroxychloroquine as postexposure prophylaxis for Covid-19. The study enrolled 821 asymptomatic adults who had high-risk or moderate-risk exposure to a confirmed Covid-19 case within 4 days. Participants were randomly assigned to receive either hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days) or a placebo. The primary outcome was the incidence of laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. The results showed no significant difference in the incidence of new illness compatible with Covid-19 between the hydroxychloroquine group (11.8%) and the placebo group (14.3%), with an absolute difference of −2.4 percentage points (P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. The study concluded that hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.