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Objectives: To assess the efficacy and safety of hydroxychloroquine (HCQ) compared with no treatment in healthcare workers with mild SARS-CoV-2 infection. Methods: Prospective, non-randomized study. All health professionals with confirmed COVID-19 between April 7 and May 6, 2020, non-requiring initial hospitalization were asked to participate. Patients who accepted treatment were given HCQ for five days (loading dose of 400 mg q12h the first day followed by200 mg q12h). Control group included patients with contraindications for HCQ or who rejected treatment. Study outcomes were negative conversion and viral dynamics of SARS-CoV-2, symptoms duration and disease progression. Result: Overall, 142 patients were enrolled: 87 in treatment group and 55 in control group. The median age was 37 years and 75% were female, with few comorbidities. There were no significant differences in time to negative conversion of PCR between both groups. The only significant difference in the probability of negative conversion of PCR was observed at day 21 (18.7%, 95%CI 2.0−35.4). The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups. A non significant reduction in duration of some symptoms in HCQ group was observed. Two patients with HCQ and 4 without treatment developed pneumonia. No patients required admission to the Intensive Care Unit or died. About 50% of patients presented mild side effects of HCQ, mainly diarrhea. Conclusions: Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19.