The implementation of health information technology interventions is at the forefront of most policy agendas internationally. However, such undertakings are often far from straightforward as they require complex strategic planning accompanying the systemic organizational changes associated with such programs. Building on our experiences of designing and evaluating the implementation of large-scale health information technology interventions in the USA and the UK, we highlight key lessons learned in the hope of informing the on-going international efforts of policymakers, health directorates, healthcare management, and senior clinicians.