Clinical trials of anticoagulants often exclude special populations. We assessed the proportion of special populations in real-world orthopedic surgery and the incidence of venous thromboembolism (VTE)-related outcomes. Data on patients with hip (n = 11 483) or knee replacement (n = 19 390) were extracted from IMS' PharMetrics Patient-Centric Database. There was high prevalence of patients aged ≥75 years (20.3%), CYP3A4-inhibitor use (21.5%), and chronic warfarin use (9.5%). Venous thromboembolism events were increased with each increasing year of age (hip: odds ratio [OR] 1.02, 95% confidence interval [CI] = 1.01-1.03; knee: OR 1.01, 95%CI = 1.00-1.02) and chronic warfarin use (hip: OR 1.56, 95%CI = 1.13-2.17; knee: OR 1.33, 95%CI = 1.03-1.72); in hip patients with renal insufficiency (OR1.61, 95%CI=1.11-2.36); and in knee patients with atrial fibrillation (OR 1.41, 95%CI = 1.06-1.88). Major bleeding was higher in hip patients with hepatic impairment (OR 21.99, 95%CI = 2.04-236.62), each increasing year of age (OR 1.08, 95%CI = 1.01-1.15), and chronic warfarin use (OR 7.11, 95%CI = 1.16-43.46). Special populations are prevalent in real-world orthopedic surgery, which may impact VTE-related outcomes.