BACKGROUND Several sclerosing agents are used to treat chronic venous diseases. Although they do not seem to differ in terms of efficacy, their safety profiles might differ. OBJECTIVE To compare the safety profile of sclerosing agents through an analysis of the World Health Organization pharmacovigilance database. METHODS The authors performed a disproportionality analysis using the proportional reporting ratio (PRR) method to compare pharmacovigilance signals between each sclerosing agent among 6 adverse event syndromes of interest: hypersensitivity reactions, arterial thromboembolic disorders, venous thromboembolic disorders, cardiac arrhythmias, visual/neurological disturbances, and skin ulcerations. The cutoff for signal detection was defined by a logPRR lower boundary 95% confidence interval (CI) ≥0 and number of cases n ≥3. RESULTS Of 1,227 Individual Case Safety Reports (ICSRs) identified, after removal of ICSRs with unselected indications, the authors selected 472 reports for the analysis. The authors found that polidocanol is associated with more reporting of venous embolic/thrombotic events (logPRR = 1.38 [95% CI 1.27–1.49]), ethanolamine with the higher pharmacovigilance disproportionality signal of cardiac arrhythmias (logPRR = 0.80 [95% CI 0.51–1.09]), and STS with more reporting of allergic reactions (logPRR = 1.79 [95% CI 1.59–1.98]). CONCLUSION The safety profile of sclerosing agents significantly differs and should guide benefit-risk ratio assessment of such agents.