We assessed the uptake of COVID-19 vaccination in a community-recruited sample of people who inject drugs (PWID) in San Francisco in 2022. Overall, 72.4% (95% CI 64.6–80.3) were vaccinated for COVID-19. Independent predictors of vaccination were age 65 years and older (adjusted odds ratio [AOR] 9.7, 95% CI 2.2–28.7) and ever testing positive for COVID-19 (AOR 2.0, 95% CI 1.2–3.5). Homelessness was associated with lower COVID-19 vaccination (AOR 0.5, 95% CI 0.3–0.8). Our study underscores the urgent need for targeted interventions to address unique challenges faced by PWID in accessing COVID-19 vaccination, particularly for those experiencing homelessness and who are younger.