District hospitals regularly experience a high incidence of substance use disorders, but rarely provide interventions. We describe the effectiveness of an intervention developed and implemented by a Western Cape hospital. Patients with probable substance use were referred to an on-site social worker for an alcohol, smoking and substance involvement screening test (ASSIST), a brief motivational intervention and referral to specialist care. At the 3-month follow-up, the ASSIST was re-administered telephonically. An intervention was received by 127 patients. A significant reduction in substance use was reported in 92 patients who completed a 3-month follow-up evaluation (p<0.001). Of the 60 patients referred to further care, half entered treatment. We conclude that, with minimal resourcing, it is feasible to administer a brief substance use intervention for patients attending district hospitals.