It is unclear whether thromboprophylaxis produces a consistent risk reduction in different subgroups of medical patients at risk from venous thromboembolism. We performed a retrospective, post hoc analysis of 3706 patients enrolled in the PREVENT study. Patients were at least 40 years old with an acute medical condition requiring hospitalization for at least 4 days and had no more than 3 days of immobilization prior to enrolment. Patients received either subcutaneous dalteparin (5000 IU) or placebo once daily. The primary end point was the composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism, asymptomatic proximal DVT, or sudden death. Primary diagnosis subgroups were acute congestive heart failure, acute respiratory failure, infectious disease, rheumatological disorders, or inflammatory bowel disease. All patients, except those with congestive heart or respiratory failure, had at least one additional risk factor for venous thromboembolism. A risk reduction was shown in patients receiving dalteparin versus placebo. The relative risk (RR) was 0.73 in patients with congestive heart failure, 0.72 for respiratory failure, 0.46 for infectious disease, and 0.97 for rheumatological disorders. The RR was 0.52 in patients aged ≥ 75 years, 0.64 in obese patients, 0.34 for patients with varicose veins, and 0.71 in patients with chronic heart failure. No subgroup had a significantly different response from any other. Importantly, multivariate analysis showed that all patient groups benefited from thromboprophylaxis with dalteparin. Our findings, therefore, support the broad application of thromboprophylaxis in acutely ill hospitalized medical patients.