Background Complementary and Alternative Medicine (CAM)are used for health promotion and disease treatment. Many options of CAM are exist. Methods Comparative cross-sectional studyamong residents of Yoruba and Hausa ethnicity in Ibadan, Nigeria.WHO modified cluster sampling technique wasused to select 800 respondents, 400 from each study groups. Data were collected using semi-structured, interviewer administered questionnaire. Results Lifetime CAM use was reported by 88.5% of Yoruba and 95.8% of Hausa respondents (p < 0.05) while 75.0% of Yoruba and 88.0% of Hausa were current CAM users (p < 0.05). The most commonly used CAM were unprocessed herbal preparations by 64.0% of Yoruba and 79.5% of Hausa respondents (p < 0.05). Conditions for which respondents used unprocessed herbal preparation included febrile illnesses (Yoruba 45.1%, Hausa 41.9%), gastrointestinal conditions (Yoruba 4.9%, Hausa 4.7%), musculoskeletal conditions (Yoruba 2.8%, Hausa 2.2%) as well as for health promotion (Yoruba 4.9%, Hausa 1.6%); there was no statistical difference. Predictors of lifetime CAM use were: being currently married [OR 2.22; 95% CI 1.46-3.39], Islamic religion [OR 1.63; 95% CI 1.02-2.62] and Hausa ethnicity [OR 2.24; 95% CI 1.02-4.93]. Similarly, the predictors of current CAM use were being currently married [OR 2.77; 95% CI 1.49-5.16], Islamic religion [OR 2.70; 95% CI 1.35-5.41] and Hausa ethnicity [OR 1.38; 95% CI 1.00-2.13]. Conclusion A high prevalence of CAM use was reported in both study groups. The conditions for which CAM was used were not significantly different.