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In Ghana, as with other developing countries, there are several health information technology (HIT) initiatives as interventions to improve healthcare delivery. HIT implementation undoubtedly results in change. However, most studies relating to HIT implementation readiness have constantly neglected the role of change in successfully implementing HIT. This study intends to identify factors affecting successful change management as part of preparation towards successfully implementing HIT in public hospital in Ghana. To carry out this study, we conducted in-depth interviews with a matrix of HIT senior managers and thematically analyzed the data. The data was transcribed and uploaded into a Nvivo 11 software for analysis using thematic analysis techniques. Five (5) themes were discovered. They are: 1) Stakeholder participation; 2) Proof of experience in similar project; 3) Availability of committed change agents/all-levels-change representatives; 4) Clearly articulated change implementation strategy; and 5) Training and improvement mechanism (post-implementation). A fresh call is made for more attention to be paid to change as part of preparatory measures towards the adoption of HIT in Ghana using the five cardinal approaches identified as a guide.