Objectives The study assessed physicians' perceptions of HIV/AIDS patients and identi- fied the determinants of physicians' attitudes toward communication with HIV/AIDS patients in Ile-Ife, Nigeria. Methods A semi-structured questionnaire was used to elicit information from 110 physi- cians in a cross-sectional survey, while in-depth interviews were conducted with 10 people living with HIV/AIDS (PLWHA) who had been previously admitted under the care of the physicians. Univariate, bivariate and multivariate analyzes were conducted. Results Although most physicians perceived PLWHA positively and 58% of them displayed a positive attitude toward communication with PLWHA under their care, the expectations of the patients concerning HIV/AIDS communication were not being met. Only 43% of physicians expressed any degree of comfort engaging PLWHA in lengthy discussions or communicating the diagnosis of HIV to patients. The strongest correlates of physicians' positive attitude were previous exposure to HIV/AIDS counseling, the number of HIV/AIDS patients treated per month, the number of years spent in the care of PLWHA, and the gender of the physicians (p5 0.05). Conclusions Physicians in Ile-Ife, Nigeria are not adequately equipped by way of training to effectively meet the expectations of their patients concerning HIV/AIDS communication. The large number of PLWHA in the country calls for urgent attention to address this important aspect of care.