Quality improvement collaboratives (QICs) are a widely applied strategy for implementing change in health care organizations. Alternative collaborative methodologies were compared to gain insight into the elements important for QIC success.A modified version of a previously described QIC evaluation tool was used to assess the methods and characteristics of the Medication Error Prevention Initiative (MEPI) and to compare MEPI with two other long-term ongoing QICs—the Vermont-Oxford Network’s Neonatal Intensive Care QIC and the Northern New England Cardiovascular Disease Study Group, and the shorter-term Breakthrough Series QICs of the Institute for Healthcare Improvement (IHI).The modified QIC assessment tool was a useful framework for QIC assessment and comparison. The MEPI differed in scope of topic, team members, and the method for learning about and making improvements.Long-term QIC methods such as those used by MEPI may be particularly applicable when QICs address broad, complex, comprehensive, or organizationwide improvement needs.