Background: Organizationally based, disease-targeted collaborative quality improvement efforts are widely applied but have not been subject to rigorous evaluation. We evaluated the effects of the Institute of Healthcare Improvement’s Breakthrough Series (IHI BTS) on quality of care for chronic heart failure (CHF). Research Design: We conducted a quasi-experiment in 4 organizations participating in the IHI BTS for CHF in 1999-2000 and 4 comparable control organizations. We reviewed a total of 489 medical records obtained from the sites and used a computerized data collection tool to measure performance on 23 predefined quality indicators. We then compared differences in indicator performance between the baseline and postintervention periods for participating and nonparticipating organizations. Results: Participating and control patients did not differ significantly with regard to measured clinical factors at baseline. After adjusting for age, gender, number of chronic conditions, and clustering by site, participating sites showed greater improvement than control sites for 11 of the 21 indicators, including use of lipid-lowering and angiotensin converting enzyme inhibition therapy. When all indicators were combined into a single overall process score, participating sites improved more than controls (17% versus 1%, P < 0.0001). The improvement was greatest for measures of education and counseling (24% versus -1%, P < 0.0001). Conclusions: Organizational participation in a common disease-targeted collaborative provider interaction improved a wide range of processes of care for CHF, including both medical therapeutics and education and counseling. Our data support the use of programs like the IHI BTS in improving the processes of care for patients with chronic diseases.