OBJECTIVE: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa. DESIGN: We conducted an open-label, individually randomized clinical trial. METHODS: Using a two-armed approach, PWH who smoke were randomized to receive either intensive antismoking behavioral counselling or intensive antismoking behavioral counseling plus c-NRT (nicotine patches augmented by nicotine gum). Self-reported smoking abstinence was biochemically validated with exhaled breath carbon monoxide (CO) and urine cotinine at 6 months. Recruitment, provision of trial interventions, and follow-up of participants took place in March 2014 through June 2016. RESULTS: We randomly assigned 280 participants to the behavioral counseling arm and 281 participants to the behavioral counseling + c-NRT arm. Four hundred and thirty-eight (78%) participants were men and 123 (22%) were women. For our primary outcome of biochemically verified abstinence at 6 months, 41 (15%) were quit in the behavioral counseling + c-NRT arm vs. 28 (10%) in the behavioral counseling arm, resulting in a 5% [95% confidence interval (CI) -1 to 10%] absolute difference in relative risk and an adjusted odd ratio of 1.47 (95% CI 0.86-2.52) comparing the behavioral counseling + c-NRT to the behavioral counseling arm. CONCLUSION: Although our results did not reach statistical significance, we found augmentation of behavioral counseling with c-NRT to increase smoking abstinence at 6 months, which is consistent with performance in the general population. PWH in low-resource settings may benefit from the addition of c-NRT to existing tobacco cessation interventions.