Computer simulation of clinical encounters is increasingly used in clinical settings to train patient work-up. The aim of this prospective, controlled study was to compare the characteristics of data collection and diagnostic exploration of physicians working up cases with a standardized patient and in a computerized simulation. Six clinicians of different clinical experience in internal medicine worked up three cases with a standardized patient and through a computer simulation allowing free inquiry. After each encounter, we asked the subjects to justify the information collected and to comment on their working diagnoses. The characteristics of data collected and working diagnoses generated were assessed and compared, according to the simulation method used. In the computer simulation, physicians limited their data collection and focused earlier and more specifically on information and working diagnoses with high levels of relevance. They reached a similar diagnostic accuracy and made decisions of a similar relevance. Computer simulation with a free-inquiry approach reproduces the data collection and the diagnostic exploration observed in a standardized-patient simulation and promotes an early collection of relevant data. Its contribution to extend the competence of learners in clinical settings should be further evaluated.