Poor usability of clinical information systems delays their adoption by clinicians and limits potential improvements to the efficiency and safety of care. Recurring usability evaluations are therefore, integral to the system design process. We compared four methods employed during the development of outpatient clinical documentation software: clinician email response, online survey, observations and interviews. Results suggest that no single method identifies all or most problems. Rather, each approach is optimal for evaluations at a different stage of design and characterizes different usability aspect. Email responses elicited from clinicians and surveys report mostly technical, biomedical, terminology and control problems and are most effective when a working prototype has been completed. Observations of clinical work and interviews inform conceptual and workflow-related problems and are best performed early in the cycle. Appropriate use of these methods consistently during development may significantly improve system usability and contribute to higher adoption rates among clinicians and to improved quality of care.