Summary. Background: Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. Patients and Methods: Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50–100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. Results: As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50–100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50–100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50–100 kg (odds ratio 2.2; 95% CI: 1.2–4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50–100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. Conclusions: Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50–100 kg.