BACKGROUND: Antiretroviral therapy (ART) for HIV, taken daily, is an effective strategy to clinically suppress the virus, providing the dual benefit of improved survival and vastly decreasing the risk of transmission. However, this highly effective intervention has not yet reached all who could benefit. Cash transfers are increasingly recognized as an effective strategy to motivate behavior change and improve HIV care and treatment outcomes, including engagement in HIV care and adherence to ART. Despite a growing evidence base and strong theoretical foundation for the cash transfer approach, key questions remain. To address these questions and begin to bridge the "know-do gap" with respect to cash transfers, our team is employing an implementation science approach to iterative development of an incentive-based intervention to promote ART uptake and adherence among people living with HIV (PLHIV) in the Lake Zone region, Tanzania. METHODS: We will conduct a type I hybrid implementation-effectiveness trial to test the effectiveness of a cash transfer intervention on the outcome of HIV viral suppression, and concurrently examine the potential for real-world implementation with a mobile health technology (mHealth) system. Specifically, our team will expand the intervention to 32 clinics and enroll 1984 PLHIV to (a) evaluate its effectiveness by conducting a cluster randomized controlled trial with clinics as the unit of randomization and 12-month viral suppression as the primary outcome and (b) evaluate the implementation challenges and successes at multiple levels (patient, provider, clinic). DISCUSSION: This trial will provide evidence not only about the real-world effectiveness of cash transfers for retention in HIV care and viral suppression, but also on the implementation challenges and successes that will facilitate or hinder wider scale-up within Tanzania and beyond. TRIAL REGISTRATION: ClinicalTrials.gov NCT04201353 . Registered on December 17, 2019.