Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The study purpose is to assess efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response. During phase 1, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in Phase 2 to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically-verified smoking reduction and 7-day abstinence prevalence at post-treatment, 6-month and 12-month follow-up. Phase 1 responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6- and 12-months) if they received low-magnitude incentives. Notably, initial exposure to CM vs. SoC did not increase rate of phase 1 response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early treatment non-responders. Weekly CM sessions in the first four weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation. This represents the first trial to examine the use of contingency management for smoking cessation among people with HIV within the context of a Sequential Multiple Assignment, Randomized Trial (SMART) design.