The objective of this study was to identify participant and environment variables that affect pharmacist–patient communication, and test their effects in a range of community pharmacy practices. Data were collected through unobtrusive observation, patient interviews, and pharmacist interviews in 12 community pharmacies. Random samples of 30 patients who received a prescription from a participating pharmacist were selected at each of the 12 pharmacies, yielding a total sample size of 360 patients. Relationships for Pharmacist Counselor Role Orientation, Patient Counselee Role Orientation, Lack of Time, Patient Privacy, Prescription Transfer by the Pharmacist, and Importance of Information with Occurrence of Communication, were tested using logistic regression analysis. Relationships among the independent variables with Length and Content of Communication were tested using multiple regression analysis. Of the 360 patients who were observed and asked to participate in an interview, 304 (84%) provided usable responses. Significant relationships (P < 0.01) were found for Prescription Transfer by the Pharmacist and Importance of Information with Occurrence of Communication. Prescription Transfer by the Pharmacist was found to be a mediating variable for Counselor Role Orientation, Importance of Information, and Lack of Time with Occurrence of Communication. Multiple regression analysis results showed positive relationships for Importance of Information and Patient Counselee Role Orientation with Length and Content of Communication. The results can be used for improving communication between pharmacists and patients to foster appropriate medication use by patients.