Widespread implementation and use of electronic health record (EHR) systems has been recognized by healthcare leaders as a cornerstone strategy for systematically reducing medical errors and improving clinical quality. However, EHR adoption requires a significant capital investment for healthcare providers, and cost is often cited as a barrier. Despite the capital requirements, a true business case for EHR system adoption and implementation has not been made. This is of concern, as the lack of a business case can influence decision making about EHR investments. The purpose of this study was to examine the role of business case analysis in healthcare organizations' decisions to invest in ambulatory EHR systems, and to identify what factors organizations considered when justifying an ambulatory EHR. Using a qualitative case study approach, we explored how five organizations that are considered to have best practices in ambulatory EHR system implementation had evaluated the business case for EHR adoption. We found that although the rigor of formal business case analysis was highly variable, informants across these organizations consistently reported perceiving that a positive business case for EHR system adoption existed, especially when they considered both financial and non-financial benefits. While many consider EHR system adoption inevitable in healthcare, this viewpoint should not deter managers from conducting a business case analysis. Results of such an analysis can inform healthcare organizations' understanding about resource allocation needs, help clarify expectations about financial and clinical performance metrics to be monitored through EHR systems, and form the basis for ongoing organizational support to ensure successful system implementation.