The contemporary causes of post-operative mortality among patients who undergo orthopedic surgery are not well characterized. The objective of this study was to determine the epidemiology of post-operative complications among orthopedic surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication. VISION was a prospective cohort study of adult patients undergoing non-cardiac surgery across 28 centres in 14 countries, who were followed for 30 days after surgery.1 For the subset of orthopedic surgery patients, a Cox proportional hazards model was used to determine time-dependent associations between various surgical complications and 30-day post-operative mortality. Preoperative and surgical variables demonstrating associations with mortality in previous VISION analyses were included as independent variables to adjust for confounding. Results from analyses were reported as hazard ratios (HR) with 95% confidence intervals (CI). Among 8385 patients who underwent an orthopedic surgery and were included in the VISION study, 132 (1.6%) patients died within 30 days of surgery. Of these deaths, 84 (63.6%) occurred in hospital during the index hospitalization, while the remaining 48 (36.4%) deaths occurred after discharge and within 30 days of the follow-up period. Incidence of death occurred as follows across the subcategories of orthopedic surgery: above knee amputation (30/221, 13.6%), internal fixation of femur (29/750, 3.9%), lower leg amputation (9/252, 3.6%), major hip or pelvic surgery (49/2898, 1.7%), major spine surgery (8/1405, 0.6%), and knee arthroplasty (7/2876, 0.2%). Six post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, infection without sepsis, sepsis, stroke, atrial fibrillation) were independently associated with death. Complications associated with the largest attributable fraction of post-operative mortality (i.e., proportion of deaths in the cohort that can be attributed to each complication, if causality were established2) were MINS (N=1454, 17.3%, HR 2.08, 95%CI 1.38-3.14, p < 0 .001, attributable fraction 20.7%), major bleeding (N=2422, 28.9%, HR 1.95, 95%CI 1.34-2.85, p < 0 .001, attributable fraction 16.5%), and sepsis (N=318, 3.8%, HR 6.24, 95%CI 3.85-10.12, p < 0 .001, attributable fraction 9.7%). The complications most associated with 30-day mortality following orthopedic surgery were MINS, major bleeding, and sepsis. These findings highlight areas for further study to identify potential interventions to mitigate perioperative mortality in orthopedic surgery and emphasizes the importance of appropriate work-up and management of MINS.3