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Although venous thromboembolism (VTE) is one of the most common and most preventable complications of hospital stay, review of the literature demonstrates large evidence-care gaps for VTE prevention.This study aimed to determine if a multi-component quality improvement (QI) strategy, including the support of hospital leadership, use of order sets, audit and feedback, and active pharmacy involvement, could increase the use of appropriate thromboprophylaxis in patients hospitalized for hip fracture surgery (HFS), major general surgery (MGS) and acute medical illness (MED).TOPPS was a cluster randomized trial involving eight hospitals. After a baseline data collection phase, one of the three patient groups at each site was randomized to the targeted QI intervention while the other two groups served as controls. In the next phase, an additional patient group at each site was randomized to the intervention while the third group remained controls. Standardized chart audits were conducted to assess the rates of appropriate thromboprophylaxis use.At baseline, the rates of appropriate thromboprophylaxis were 79% in HFS, 43% in MGS and 31% in MED. By the end of phase 3, 89% of HFS, 65% of MGS and 70% of MED patients were receiving appropriate prophylaxis. Improvement was greater in the intervention groups compared to controls (85% vs. 76% in HFS; 67% vs. 54% in MGS; 64% vs. 62% in MED) and this difference reached significance in the MGS group (p = 0.048).Use of a multi-component intervention can be effective in improving the appropriate use of thromboprophylaxis.This study assessed the impact of a multicomponent intervention on prophylaxis for hospitalized patients at risk of venous thromboembolism (VTE).The intervention involved pharmacists acting as reminders and assisting in the development of order sets with embedded VTE prophylaxis.Rates of thromboprophylaxis improved across all groups (General Internal Medicine, General Surgery and Hip Fracture Surgery).Greater improvement was seen in the intervention versus control groups.