ABSTRACT. Objective: This research studied the relationships of the components of entrepreneurial strategic orientation (ESO) with implementation of electronic health records (EHRs) within organizations that treat patients with substance use disorders (SUDs). Method: A national sample of 317 SUD treatment providers were studied in a period after the Health Information Technology for Economic and Clinical Health (HITECH) Act was enacted (2009) and meaningful use EHR requirements were established (2010), but before implementation of the Affordable Care Act. The study sample was selected using stratified random sampling and was part of a longitudinal study of treatment providers across the United States. Results: After we controlled for potentially confounding variables, four components of ESO had a significant relationship with EHR implementation. Levels of slack resources in an organization moderated the relationship of ESO with meaningful use of EHRs, increasing the strength of the relationship for some components but reducing the strength of others. Conclusions: From a policy and practice perspective, the results suggest that training and education to develop higher levels of ESO within SUD treatment organizations are likely to increase their level of meaningful use of EHRs, which in turn may enhance the integration of SUD treatment with primary medical providers, better preparing SUD treatment providers for the environmental changes of the Affordable Care Act. (J. Stud. Alcohol Drugs, 76, 942-951, 2015)