Background: High prevalence rates of hazardous and harmful alcohol use have been found in a hospital outpatient setting in South Africa. Hospital settings are a particularly valuable point of contact for the delivery of brief interventions because of the large access to patient populations each year. With this in mind, the primary purpose of this randomized controlled trial is to provide screening for alcohol misuse and to test the effectiveness of brief interventions in reducing alcohol intake among hospital outpatients in South Africa. Methods. The study design for this effectiveness study is a randomized controlled trial with 6- and 12-month follow-ups to examine the effects of a brief alcohol intervention to reduce alcohol use by hazardous or harmful drinkers in a hospital setting. Outpatients were screened for alcohol problems, and those identified as hazardous or harmful drinkers were randomized into an experimental or control group. The experimental group received one brief counselling session on alcohol risk reduction, while the control group received a health education leaflet. Results: Of the 1419 screened for alcohol misuse who agreed to participate in the trial 392 (27.6%) screened positive for hazardous or harmful use on the Alcohol Use Disorder Identification Test (AUDIT) (score 7/8-19) and 51 (3.6%) had an AUDIT score of 20 or more. Among the 282 (72%) hospital outpatients who also attended the 12-month follow-up session, the time effects on the AUDIT scores were significant [F (1,195 = 7.72), P < 0.01] but the intervention effect on the AUDIT score was statistically not significant [F (1,194 = 0.06), P < 0.804]. Conclusion: Given the lack of difference in outcome between control and intervention group, alcohol screening and the provision of an alcohol health education leaflet may in itself cause reduction in drinking. Trial registration. PACTR201110000319392.