Objective:The primary objective of this systematic review and meta-analysis was to elucidate the rate of venous thromboembolism (VTE) after endovenous interventions for varicose veins in the presence of pharmacological and mechanical thromboprophylaxis versus mechanical thromboprophylaxis alone.Background:The VTE rate after endovenous procedures for varicose veins is higher than other day-case procedures and could be reduced with pharmacological thromboprophylaxis.Methods:The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines with a registered protocol (PROSPERO: CRD42021274963). Studies of endovenous intervention for superficial venous incompetence reporting the predefined outcomes with at least 30 patients were eligible. Data were pooled with a fixed effects model.Results:There were 221 trials included in the review (47 randomized trial arms, 105 prospective cohort studies, and 69 retrospective studies). In randomized trial arms, the rate of deep venous thrombosis with additional pharmacological thromboprophylaxis was 0.52% (95% CI, 0.23%–1.19%) (9 studies, 1095 patients, 2 events) versus 2.26% (95% CI, 1.81%–2.82%) (38 studies, 6951 patients, 69 events) with mechanical thromboprophylaxis alone. The rate of pulmonary embolism in randomized trial arms with additional pharmacological thromboprophylaxis was 0.45% (95% CI, 0.09–2.35) (5 studies, 460 participants, 1 event) versus 0.23% (95% CI, 0.1%–0.52%) (28 studies, 4834 participants, 3 events) for mechanical measures alone. The rate of EHIT grade III to IV was 0.35% (95% CI, 0.09–1.40) versus 0.88% (95% CI, 0.28%–2.70%). There was 1 VTE-related mortality and 1 instance of major bleeding, with low rates of minor bleeding.Conclusions:There is a significant reduction in the rate of DVT with additional pharmacological thromboprophylaxis and routine prescription of anticoagulation after endovenous varicose vein intervention should be considered. VTE risk for individual study participants is heterogeneous and risk stratification in future randomized interventional studies is critical to establish the clinical effectiveness and safety of additional pharmacological thromboprophylaxis.