<h3>Background</h3> Antimalarials (AMs) have shown to exert a thromboprotective effect in SLE patients, but studies thus far have been limited to North American and European patients. This study was conducted to assess whether a similar effect is observed in Latin American SLE patients. <h3>Materials and methods</h3> SLE patients with a recent diagnosis (≤2 years) recruited and followed longitudinally as part of the GLADEL cohort were examined to establish risk factors for thrombotic events (TEs) and the possible preventive role of AMs. The end-point of this study was thrombosis defined as either arterial or venous occurring after entry into the cohort. Independent variables included were socio-demographic characteristics, clinical manifestations as measured by the ACR classification criteria, laboratory, history of previous TEs and hospitalisation. For descriptive purposes, patients were divided according to use or non-use of an AMs agent (chloroquine and/or hydroxychloroquine) based on each patient's entire follow-up period during the study. Patients were classified as "users" if they had received AMs for at least 6 months, whereas "non-users" comprised patients who had received AMs for less than 6 months or who had never received them. Treatment with AMs, glucocorticoids and anticoagulants along with hospitalizations were considered as time-dependent covariates. The effect of AM use on thrombosis after adjustment for potential confounders (variables known to affect thrombosis and the use of AMs) was examined using a multivariable Cox regression model. A backward selection algorithm was used to select the variables retained in the model with α-level to stay in the model set to 0.05. <h3>Results</h3> Of the 1,480 patients included in the GLADEL cohort, 1,208 (82%) were considered AMs users with median exposure time of 42.1 months (Q1–Q3: 19.1–62.3). TEs occurred in 103 (7%) of the patients during a median follow up time since enrolment of 15.4 months (Q1–Q3: 4.6–38.2). The rate of thrombosis for AM users was 1.44 per 100 patient/years of follow-up vs. 3.01 for non-AM users (HR 0.55, 95% CI: 0.37–0.82). After adjusting for potential confounders in the Cox proportional hazards regression model, the use of AMs was associated with a 43% reduction in the thrombosis rate (HR 0.57, 95% CI: 0.38–0.85). Other variables significantly associated with TEs are depicted in Table 1. <h3>Conclusions</h3> After adjusting for possible confounding factors related to AMs use, a clear protective effect of AMs in the development of TEs in SLE patients from this Latin American cohort was observed. <h3>Acknowledgements</h3> On behalf of the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort.