Background The literature on implementing Electronic Health Records (EHR) in hospitals is very diverse. The objective of this study is to create an overview of the existing literature on EHR implementation in hospitals and to identify generally applicable findings and lessons for implementers. Methods A systematic literature review of empirical research on EHR implementation was conducted. Databases used included Web of Knowledge, EBSCO, and Cochrane Library. Relevant references in the selected articles were also analyzed. Search terms included Electronic Health Record (and synonyms), implementation, and hospital (and synonyms). Articles had to meet the following requirements: (1) written in English, (2) full text available online, (3) based on primary empirical data, (4) focused on hospital-wide EHR implementation, and (5) satisfying established quality criteria. Results Of the 364 initially identified articles, this study analyzes the 21 articles that met the requirements. From these articles, 19 interventions were identified that are generally applicable and these were placed in a framework consisting of the following three interacting dimensions: (1) EHR context, (2) EHR content, and (3) EHR implementation process. Conclusions Although EHR systems are anticipated as having positive effects on the performance of hospitals, their implementation is a complex undertaking. This systematic review reveals reasons for this complexity and presents a framework of 19 interventions that can help overcome typical problems in EHR implementation. This framework can function as a reference for implementers in developing effective EHR implementation strategies for hospitals.