Little is known about unwarranted clinical practice variations within US hospitals. The objectives of this study were to investigate whether hospitals are concerned about variations and their experiences with strategies to reduce variations. Case studies were conducted at 5 hospitals, and a survey of acute care hospitals was conducted in 4 states. Each of the case studies presented a different experience. Unwarranted variations were a concern for 90% of survey respondents, with no differences by state (P = .7) or hospital size (P = .2). Of these, 75% had a strategy in place to reduce variation. The likelihood of a multipronged approach was significantly higher in larger hospitals (P = .0009). This study revealed disparate approaches to reducing unwarranted clinical practice variations and also highlighted barriers to reducing variation. The case studies identified some models that could be emulated, but questions remain about whether there is a single best way forward.