Abstract: The n e w e ng l a n d j o u r na l of m e dic i n e Original Article A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 D.R. Boulware, M.F. Pullen, A.S. Bangdiwala, K.A. Pastick, S.M. Lofgren, E.C. Okafor, C.P. Skipper, A.A. Nascene, M.R. Nicol, M. Abassi, N.W. Engen, M.P. Cheng, D. LaBar, S.A. Lother, L.J. MacKenzie, G. Drobot, N. Marten, R. Zarychanski, L.E. Kelly, I.S. Schwartz, E.G. McDonald, R. Rajasingham, T.C. Lee, and K.H. Hullsiek​​ A BS T R AC T BACKGROUND Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. METHODS We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. The authors’ full names, academic degrees, and affiliations are listed in the Appendix. Address reprint requests to Dr. Boulware at the University of Minnesota, 689 23rd Ave., Minneapolis, MN 55455, or at ­boulw001@​­umn​.­edu. This article was published on June 3, 2020, at NEJM.org. DOI: 10.1056/NEJMoa2016638 Copyright © 2020 Massachusetts Medical Society. RESULTS We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; 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. CONCLUSIONS After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.) n engl j med  nejm.org The New England Journal of Medicine Copyright © 2020 Massachusetts Medical Society. All rights reserved. 1 The n e w e ng l a n d j o u r na l S evere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the global, rapidly emerging virus causing coronavirus disease 2019 (Covid-19).1 The current public health strategies to mitigate transmission are rapid identification of cases, isolation, contact tracing, and..