Background Stigmatising attitudes of health care professionals towards mental illness can impede treatment provided for psychiatric patients. Many studies have reported undergraduate training to be a critical period for changing the attitudes of medical students, and one particularly valuable intervention strategy involves time spent in a clinical psychiatric rotation. In South Africa, medical students are exposed to a clinical rotation in psychiatry but there is no evidence to show whether this has an effect on attitudes toward mental illness. Methods This prospective cohort study involved a convenience sample of 112 South African medical students in their 5th or 6th year of undergraduate training. This sample attended a 7-week psychiatry rotation. The Attitudes to Mental Illness Questionnaire (AMIQ) was used to assess students’ attitudes toward mental illness before and after the clinical rotation which includes exposure to a number of psychiatric sub-divisions and limited didactic inputs. Results There was a significant improvement ( p < 0.01, t -test) in the students’ attitude toward mental illness following the psychiatric rotation. Females displayed a more positive attitude towards mental illness at the end of the rotation compared to males. The participants’ attitude significantly deteriorated for the non-psychiatric vignette describing diabetes (< 0.01, t -test). Conclusions Our findings suggest that clinical training and exposure to a psychiatric setting impacts positively on medical students’ attitude towards mental illness, even when this training does not include any focused, didactic anti-stigma input.