Abstract: MINI-REVIEW Hydroxychloroquine is effective, and consistently so when provided early, for COVID-19: a systematic review C. Prodromos1 and T. Rumschlag2 1) Illinois Sports Medicine and Orthopaedic Center and 2) Foundation for Orthopaedics and Regenerative Medicine, Glenview, IL, USA Abstract Hydroxychloroquine (HCQ) has shown efficacy against coronavirus disease 2019 (COVID-19) in some but not all studies. We hypothesized that a systematic review would show HCQ to be effective against COVID-19, more effective when provided earlier, not associated with worsening disease and safe. We searched PubMed, Cochrane, Embase, Google Scholar and Google for all reports on HCQ as a treatment for COVID-19 patients. This included preprints and preliminary reports on larger COVID-19 studies. We examined the studies for efficacy, time of administration and safety. HCQ was found to be consistently effective against COVID-19 when provided early in the outpatient setting. It was also found to be overall effective in inpatient studies. No unbiased study found worse outcomes with HCQ use. No mortality or serious safety adverse events were found. HCQ is consistently effective against COVID-19 when provided early in the outpatient setting, it is overall effective against COVID-19, it has not produced worsening of disease and it is safe. © 2020 The Authors. Published by Elsevier Ltd. Keywords: Azithromycin, COVID-19, hydroxychloroquine, outpatient, SARS-CoV-2 Original Submission: 9 September 2020; Revised Submission: 28 September 2020; Accepted: 29 September 2020 Article published online: 5 October 2020 Corresponding author: C. Prodromos, MD, 1714 N Milwaukee Av, Glenview, IL 60025, USA. E-mail: research@ismoc.net COVID-19, and that efficacy would be greater if HCQ was provided earlier in the disease course. We also hypothesized that some studies that failed to show efficacy would be biased against positive efficacy and that no unbiased studies would show worsening. Finally, we hypothesized that HCQ would be found to be safe.