BACKGROUND: Thromboprophylaxis in elderly patients, including post-acute care patients, is at variance with scientific evidence. The purpose of this study was to determine whether a multifaceted intervention was followed by a decrease in deep venous thrombosis (DVT). METHODS: A prospective preintervention-postintervention study was conducted in 1373 patients (preintervention phase, n = 709; postintervention phase, n = 664), aged 65 years or older, enrolled in 33 hospital-based post-acute care facilities in France. An evidence-based guideline addressing pharmacologic and mechanical prophylaxis was implemented through a multifaceted intervention. The main outcome measure was any DVT diagnosed at routine comprehensive ultrasonography performed by registered angiologists. RESULTS: A DVT was found in 91 patients (12.8%) in the preintervention phase and in 52 patients (7.8%) in the postintervention phase (P = .002). The decrease in DVT involved the calf (7.1% vs 3.6%; P = .005) and the proximal venous segments (5.8% vs 4.2%; P = .18) and remained significant after adjusting for risk factors (adjusted odds ratio of any DVT, 0.58; 95% confidence interval, 0.39-0.86). Pharmacologic prophylaxis with either low-molecular-weight heparin at the high-risk dose, unfractionated heparin, and vitamin K antagonist was similar in the 2 study groups, whereas patients in the postintervention group were more likely to use graduated compression stockings (27.4% vs 34.6%; P = .004) and less likely to receive low-molecular-weight heparin at the low-risk dose (24.7% vs 18.5%; P = .006), which was not recommended by our guideline. CONCLUSIONS: A multifaceted intervention addressing venous thromboembolism prophylaxis in post-acute care patients can be followed by a significant decrease in the rate of any DVT in elderly patients. More active interventions are needed to enforce compliance with evidence-based guidelines.