BACKGROUND: Given the amount of time and resources invested in implementing quality programs in hospitals, few studies have investigated their clinical impact and what strategies could be recommended to enhance its effectiveness. OBJECTIVE: To assess variations in clinical practice and explore associations with hospital- and department-level quality management systems. DESIGN: Multicenter, multilevel cross-sectional study. SETTING AND PARTICIPANTS: Seventy-three acute care hospitals with 276 departments managing acute myocardial infarction, deliveries, hip fracture, and stroke in seven countries. INTERVENTION: None. MEASURES: Predictor variables included 3 hospital- and 4 department-level quality measures. Six measures were collected through direct observation by an external surveyor and one was assessed through a questionnaire completed by hospital quality managers. Dependent variables included 24 clinical practice indicators based on case note reviews covering the 4 conditions (acute myocardial infarction, deliveries, hip fracture and stroke). A directed acyclic graph was used to encode relationships between predictors, outcomes, and covariates and to guide the choice of covariates to control for confounding. RESULTS AND LIMITATIONS: Data were provided on 9021 clinical records by 276 departments in 73 hospitals. There were substantial variations in compliance with the 24 clinical practice indicators. Weak associations were observed between hospital quality systems and 4 of the 24 indicators, but on analyzing department-level quality systems, strong associations were observed for 8 of the 11 indicators for acute myocardial infarction and stroke. Clinical indicators supported by higher levels of evidence were more frequently associated with quality systems and activities. CONCLUSIONS: There are significant gaps between recommended standards of care and clinical practice in a large sample of hospitals. Implementation of department-level quality strategies was significantly associated with good clinical practice. Further research should aim to develop clinically relevant quality standards for hospital departments, which appear to be more effective than generic hospital-wide quality systems.