Patients vary in their willingness and ability to actively participate in medical consultations. Because more active patient participation contributes to improved health outcomes and quality of care, it is important to understand factors affecting the way patients communicate with healthcare providers. The objectives of this study were to examine the extent to which patient participation in medical interactions is influenced by 1) the patient's personal characteristics (age, gender, education, ethnicity); 2) the physician's communication style (eg, use of partnership-building and supportive talk); and 3) the clinical setting (eg, the health condition, medical specialty). The authors conducted a post hoc cross-sectional analysis of 279 physician-patient interactions from 3 clinical sites: 1) primary care patients in Sacramento, California, 2) patients with systemic lupus erythematosus (SLE) from the San Francisco Bay area, and 3) patients with lung cancer from a VA hospital in Texas. The outcome measures included the degree to which patients asked questions, were assertive, and expressed concerns and the degree to which physicians used partnership-building and supportive talk (praise, reassurance, empathy) in their consultations. The majority of active participation behaviors were patient-initiated (84%) rather than prompted by physician partnership-building or supportive talk. Patients who were more active participants received more facilitative communication from physicians, were more educated, and were more likely to be white than of another ethnicity. Women more willingly expressed negative feelings and concerns. There was considerable variability in patient participation across the 3 clinical settings. Female physicians were more likely to use supportive talk than males, and physicians generally used less supportive talk with nonwhite compared with white patients. Patient participation in medical encounters depends on a complex interplay of personal, physician, and contextual factors. Although more educated and white patients tended to be more active participants than their counterparts, the strongest predictors of patient participation were situation-specific, namely the clinical setting and the physician's communicative style. Physicians could more effectively facilitate patient involvement by more frequently using partnership-building and supportive communication. Future research should investigate how the nuances of individual clinical settings (eg, the health condition, time allotted for the visit) impose constraints or opportunities for more effective patient involvement in care.