Objective: To evaluate the impact of guidelines for treatment and prophylaxis of VTE on appropriateness of anticoagulant therapy, JCAHO performance measures, adverse drug outcomes, and total cost of therapy Methods: We conducted a multihospital ‘pre-post' guideline intervention study. Guidelines for VTE treatment and prophylaxis were developed and implemented in the participating hospitals. Retrospective chart review was used to collect patient data during the pre and post periods. Results: The number of participating hospitals and total patient cases submitted by the hospitals were 23 and 617, respectively in the pre-guideline (PRG) phase and 13 and 338, respectively in the post-guideline phase (POG). The appropriateness of prescribing (as measured by the dose, duration, and the type of anticoagulant used) increased by 7% (PRG 77%, POG 84%). JCAHO performance measures for 1) percentage of VTE patients receiving education; 2) percentage of patients with reduced LMWH dosage in compromised renal failure; 3) percentage of patients with normal INR; 4) percentage of patients with objective confirmation of clinically suspected VTE; 5) percentage of unfractionated heparin (UFH) managed by nomogram/protocol; and 6) percentage of patients with anticoagulation overlap of parenteral and warfarin therapy, increased by 20%,17%, 13%, 9%, 6%, and 1%, respectively. JCAHO measures for 1) VTE treatment for discharged patients with active cancer, and 2) platelet count monitoring for patients with VTE receiving UFH, decreased by 2% and 11%, respectively. The proportion of patients experiencing at least one anticoagulant related adverse drug outcome decreased by 0.5% and rates of major bleeding decreased by 1% in POG. On average, the total cost of therapy (cost of major/minor bleeding, DVT, PE and drugs costs) decreased by $105 per patient in POG. Conclusion: Implementation of VTE treatment and prophylaxis guidelines improved appropriateness of anticoagulant therapy in the participating hospitals resulting in improved outcomes, reduced costs, and improved quality performance.