SummaryBackground Although the standard treatment for venous ulcers is compression, drugs may be used as adjunctive therapy. Simvastatin has shown potential wound-healing properties; however, no studies have investigated its use in venous ulcers. Objectives To assess the efficacy and safety of simvastatin in venous ulcer healing when combined with standard treatment for ulcers. Methods This was a randomized, double-blind, placebo-controlled trial. Outcome measures were the proportion of healed ulcers, healing time, total surface area healed and Dermatology Life Quality Index (DLQI) scores. Results Sixty-six patients were randomized into two groups: a simvastatin (n = 32) and a control (n = 34) group. Among ulcers ≤ 5 cm, 100% were healed in the simvastatin group, and 50% were healed in the control group [relative risk (RR) 0Á10, 95% confidence interval (CI) 0Á0141-0Á707]. The average healing times for ulcers ≤ 5 cm were 6Á89 AE 0Á78 weeks and 8Á40 AE 1Á13 weeks for the simvastatin and control groups, respectively (P < 0Á001). Among ulcers > 5 cm, 67% closed in the simvastatin group, with a mean healing time of 9Á17 AE 1Á07 weeks. No ulcers of this size closed in the control group (RR 0Á33, 95% CI 0Á132-0Á840). The simvastatin group had lower DLQI scores (P < 0Á001) post-treatment. No adverse effects were documented. Conclusions Simvastatin 40 mg daily, in addition to standard wound care and compression, is associated with a significant improvement in healing rate and time, as well as an improved patient quality of life when compared with placebo in the management of venous ulcers.