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Reliable prophylaxis of hospital-associated venous thromboembolism (HA-VTE) is not achieved in many hospitals. Efforts to improve prophylaxis have had uneven results.To reduce HA-VTE with a scalable quality improvement collaborative.A prospective, unblinded, open-intervention study with historical controls.All adult inpatients at 35 community hospitals in California, Arizona, and Nevada.A centrally supported collaborative implementing standardized VTE risk assessment and prophylaxis. Protocols were developed with 9 “pilot” sites, which received individualized mentoring. Finished protocols were disseminated to 26 “spread” sites, which received improvement webinars without mentoring. Active surveillance for real-time correction of suboptimal prophylaxis was funded in pilot sites and encouraged in spread sites. Planning and minimal improvement work began in 2011; most implementation occurred in 2012 and 2013.Rates of per-protocol prophylaxis (at pilot sites), and compliance with The Joint Commission VTE measures (all sites), were monitored starting in January 2012. The International Classification of Diseases, 9th Edition-Clinical Modification codes were used to determine the rates of HA-VTE within 30 days of discharge, heparin-induced thrombocytopenia, and anticoagulation adverse events; preimplementation (2011) rates were compared with postimplementation (2014) rates.Protocol-appropriate prophylaxis rates and The Joint Commission measure compliance both reached 97% in 2014, up from 70% to 89% in 2012 and 2013. Five thousand three hundred and seventy HA-VTEs occurred during 1.16 million admissions. Four hundred twenty-eight fewer HA-VTEs occurred in 2014 than in 2011 (relative risk 0.78; 95% confidence interval, 0.73–0.85). HA-VTEs fell more in pilot sites than spread sites (26% vs 20%). The rates of adverse events were reduced or unchanged.Collaborative efforts were associated with improved prophylaxis rates and fewer HA-VTEs.