Background: The treatment of substance use disorders is a public health priority, particularly in South Africa where the prevalence of these disorders is high. We tested two peer-counsellor delivered brief interventions (BIs) for risky substance use among adults presenting to emergency departments (EDs) in South Africa. Methods: In this randomised controlled trial, we enrolled patients presenting to one of three 24-hour EDs who screened at risk for substance use according to the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Eligible patients were randomly allocated to one of three conditions: Motivational Interviewing (MI), blended MI and Problem Solving Therapy (MI-PST) or a Psycho-educational Control Group (CG). The primary outcome was reduction in ASSIST scores at three months follow-up. Results: Of the 2736 patients screened, 335 met inclusion criteria, were willing to participate in the intervention and were randomised to one of three conditions: 113 to MI, 112 to MI-PST and 110 to CG. ASSIST scores at three months were lower in the MI-PST group than they were in the MI and CG groups (adjusted mean difference of -1.72, 95 % CI -3.36 - -0.08). We recorded no significant difference in ASSIST scores between the CG and MI group (adjusted mean difference of -0.02, 95 % CI -2.01 - 1.96). Conclusion: With the addition of minimal resources, BIs are feasible to conduct in EDs in a low resourced country. These preliminary findings report that MI-PST appears to be an effective BI for reducing substance use among at risk participants. Further research is required to replicate these findings with effort to limit attrition, to determine whether reductions in substance use are persistent at 6 and 12 month follow-up and whether parallel changes occur in other indications of treatment outcomes, such as injury rates and ED presentations. Trial registration: This trial registered with the Pan African Clinical Trial Registry (PACTR201308000591418).