BACKGROUND: Although older patients with restricted mobility are at increased risk for venous thromboembolism, they are under-represented in clinical trials evaluating prophylactic treatments against deep vein thrombosis (DVT). OBJECTIVE: To determine whether prolonged prophylaxis with low-molecular-weight heparin (LMWH) is associated with a lower rate of DVT in older patients with restricted mobility. METHODS: Two cross-sectional studies were conducted in 50 hospital-based, post-acute care facilities in France in 2001 and 2003. The studies included 1603 evaluable patients aged >or=65 years, including 866 LMWH users (median treatment duration 23 days; interquartile range 13-42) and 737 LMWH non-users. All patients underwent complete compression ultrasonography performed by board-certified vascular medicine physicians. The primary study outcome was proximal DVT. Propensity analyses were used to control for bias in LMWH treatment assignment. RESULTS: The rate of proximal DVT was 4% (35/866) and 5.7% (42/737) for LMWH users and non-users, respectively (p = 0.16). Prophylaxis with LMWH was associated with decreased odds of proximal DVT after adjusting for baseline characteristics (odds ratio [OR] 0.56; 95% CI 0.33, 0.95; p = 0.03) or quintile of propensity score (OR 0.58; 95% CI 0.35, 0.99; p = 0.04). In propensity matched analysis, 342 LMWH users were at decreased odds of proximal DVT compared with 342 non-users (OR 0.50; 95% CI 0.24, 1.00; p = 0.04). The decrease in proximal DVT was paralleled by a similar decrease in distal DVT. Compared with non-users, only high-risk dose users had decreased odds of DVT. CONCLUSIONs: In this observational study, prophylaxis with a high-risk dose of LMWH was associated with decreased odds of proximal DVT in older patients with restricted mobility. Further study is needed before recommending routine prophylaxis with LMWH in these patients.