This article proposes a Clinical Adoption Framework for making sense of health information system (HIS) success in Canada. It extends Canada Health Infoway's Benefits Evaluation Framework with contextual factors that influence HIS adoption by clinicians, which include people, organization, implementation, and the macro environment. Our hypothesis is that successful clinical adoption of an HIS requires explicit recognition, strategies and actions that address the factors described in the framework. Validation of this framework by stakeholders and literature has thus far been favourable. Its potential application with selected evaluation approaches in specific settings, the implications and work ahead are discussed.