People who are homeless are at increased risk of COVID-19 infection, and of poorer associated outcomes. Delivering vaccinations to, and ensuring uptake of multiple doses in, people who are homeless is complex. Financial incentives may improve vaccination uptake, particularly in people who have not received routine vaccinations previously, though evidence about the effect of incentives is limited and variable. This randomized controlled trial (ANZCTR 383156) assessed the effect of a financial incentive (an A$10 grocery voucher) on uptake of the second COVID-19 vaccination in Australian adults who were homeless, and who had received their first dose. Participants were recruited through a vaccination program for people experiencing homelessness between September 2021 and January 2022. They were followed-up for a minimum of 6.5 months. Uptake was measured ‘on-time’ at 6 weeks, and at any time during the trial period. Vaccination status was checked on the Australian Immunisation Register. Demographic and vaccination program characteristics associated with uptake were also investigated. Eighty-six people consented to participate, and 43 were randomly allocated to each of the ‘incentive’ and ‘no incentive’ groups. The incentive slightly increased the likelihood of a participant receiving a second vaccination on-time (risk difference (RD), 11.6 % [95 %CI, −9.0, 32.2 %]; p = 0.27), and at any time during the trial (RD, 14.0 % [95 %CI, –2.2, 30.1 %], p = 0.09). The incentive had a significant positive effect on uptake in people with no previous vaccination history, increasing their likelihood of receiving a second vaccination on-time (RD, 42.3 % [95 %CI, 15.7, 68.8 %]; p = 0.002) and at any time during the trial (RD, 38.7 % [95 %CI, 16.1, 61.3 %], p < 0.001). Financial incentives may increase COVID-19 vaccination uptake in people who are homeless, and particularly those who have no previous vaccination history. Future research should consider alternative incentive values, types, and cost-effectiveness.