Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997-2017). Cox regression models calculating hazard ratio (HR) analyzing the risk of MACE was performed comparing time on and off hydroxychloroquine (including never-user). The models were adjusted for age, sex, socio-economic status, concomitant treatment, and cardiovascular risk factors.Among 4587 patients with LE, 51% (n=2343) were treated with HCQ during the study period. An inverse association between use of HCQ and MACE risk was observed among patients with SLE (adjusted HR 0.65; 95% CI 0.46-0.90) and patients with CLE (adjusted HR 0.71; 95% CI 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time-control design.No information on disease activity/severity was available.Our findings indicate an opportunity to reduce risk of cardiovascular events in patients with LE through use of hydroxychloroquine.