The purpose of this study was to identify hospital organizational characteristics consistently associated with adherence to multiple clinical practice guidelines (CPGs). We examined the relationship between organizational and patient population characteristics and adherence to three screening CPGs implemented throughout the Veterans Health Administration (VHA). The study included 114 acute care facilities. Three sources of data were used: 1998 American Hospital Association data, VHA External Peer Review Program data for 1998 and 1999, and the 1999 Veterans Satisfaction Survey. Organizational characteristics likely to affect adherence with the CPGs were classified into five conceptual domains (clinical emphasis, operational capacity, patient population, professionalism, and urbanicity). Organizational characteristics were ranked, based on their standardized beta coefficients in bivariate logistic regressions predicting the likelihood of adherence. Within-domain multivariable logistic analyses assessed the robustness of individual predictors of CPG adherence, controlling for other organizational factors within the same domain. Overall, 46 of 48 relationships in the bivariate logistic analyses were significant, and 43 of these remained significant in the within-domain multivariate analyses. The relative rankings of the variables as predictors of CPG adherence within conceptual domains were also quite consistent. Strong evidence was found for the importance of specific organizational factors, including mission, capacity, professionalism, and patient population characteristics that influence CPG adherence in a large multi-institutional sample involving multiple provider practices. Research and programs to improve adherence to CPGs and other quality improvement activities in hospitals should incorporate these organizational factors.