Major ventral hernia surgeries are commonly performed. Despite guideline recommendations for chemo-thromboprophylaxis in the perioperative period, the optimal timing for its initiation is unknown. We characterized the variability in perioperative chemoprophylaxis in elective major ventral hernia surgery and determine whether timing of chemoprophylaxis affects bleeding and symptomatic venous thromboembolism.Retrospective analysis of all elective major ventral hernia surgery undertaken between January 1, 2014, and December 31, 2019, at 14 hospitals across Australia. Major bleeding was defined as the need for blood transfusion, reoperation, or20 g/L fall in hemoglobin. Clinical venous thromboembolism was defined as imaging-proven symptomatic disease30 days postsurgery. Propensity score matched analysis was used to validate primary findings.In the study, 3,384 hernia repairs were analyzed. Chemoprophylaxis was administered early (before skin closure), postoperatively, or not given in 856 (25.3%), 1,701 (50.3%), and 827 (24.4%) patients, respectively. This varied between surgeons, trainees, and institutions. Clinical venous thromboembolism occurred in 6 (0.2%) patients and was unrelated to chemoprophylaxis timing. 134 (4.0%) patients had postoperative bleeding, with 67 (50%) major bleeds, requiring surgical control in 41 (30.6%) cases. Bleeding extended duration of stay (mean [standard deviation], 7.0 (13.9) vs 2.6 (4.7) days, P.001). Notably, compared with postoperative (odds ratio 1.98; 95% confidence interval, 1.36-2.88; P.001) and no (odds ratio 2.83; 95% confidence interval, 1.70-4.89; P.001) chemoprophylaxis, early initiation significantly increased bleeding risk and independently predicted its occurrence.The incidence of clinical venous thromboembolism after elective major ventral hernia repair is low. Variability in perioperative thromboprophylaxis is high. Early chemoprophylaxis increases bleeding risk without appreciable additional protection from venous thromboembolism.