Successful implementation of healthcare information systems (HIS) is tremendously difficult. Although few is known about the mechanisms enabling successful HIS implementation, effective learning pro-cesses and consciously implemented adaptations to HIS and medical reality are assumed to be pivotal. In this paper, we aim to gain understanding about the enablers of these processes. To that end, we conducted an in-depth case study of an HIS implementation project. Findings demonstrate that the success of HIS initiatives is particularly dependent on the capacity of involved actors to integrate their idiosyncratic knowledge and to develop congruent and actionable understanding. Looking at the conducting paths for integrating knowledge, our findings further show that stakeholders’ social capital reflected by their opportunity, motivation and ability to capitalize on existing knowledge and experiences are critical for aligning HIS and medical reality. Taking a qualita-tive approach, we extend existing research by illustrating how social capital and knowledge integration outcomes coevolve. Overall, our results highlight the importance of social capital for knowledge integration during HIS initiatives. Medical and IT professionals’ collaborative endeavours seem to produce valuable solutions that balance divergent stakeholders’ concerns when opportunity, motivation and ability to integrate their knowledge, expertise and interests are effectively managed.