Venous thromboembolism (VTE) is a potentially fatal disease. Important risk factors of a provoked VTE are trauma, surgery or immobilization. Especially, patients who undergo hip and knee replacements are at high risk for postoperative VTE. We aimed to compare in-hospital VTE burden and other outcomes after upper and lower extremity endoprosthetic surgeries in Germany. The nationwide German inpatient sample of the years 2005-2015 was used for data analysis. Patients who underwent endoprosthetic joint/bone replacements of the extremities (OPS codes 5-820, 5-822, 5-824 and 5-826) were further stratified in those operated on lower (OPS codes 5-820, 5-822 and 5-826) or upper extremity (OPS code 5-824) joints. Patients operated at upper and lower extremity were compared and lower extremity endoprosthetic surgery was investigated as a predictor for adverse outcomes. Overall, 4,134,088 hospitalized patients with extremity joint endoprosthetic surgeries (64.3% females, 54.0% aged > 70 years) were included in our analysis. Of these, 3,950,668 patients (95.6%) undergo lower and 183,420 (4.4%) upper extremity endoprosthetic joint surgery. VTE [RR 2.60 (95% CI 2.41-2.79), P < 0.001] and all-cause death [RR 1.68 (95% CI 1.58-1.77), P < 0.001] were more common in patients with lower extremity joint surgery. Risk for VTE events [OR 2.69 (2.50-2.90), P < 0.001] and in-hospital death [OR 1.65 (1.56-1.75), P < 0.001] were both higher in lower than in upper extremity joint surgeries independently of age, sex and comorbidities. Patients who undergo lower extremity endoprosthetic joint surgeries, bear a higher risk for VTE and in-hospital death compared to those with upper extremity endoprosthetic joint surgeries.