BackgroundPeople who inject drugs (PWID) are vulnerable to acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examined correlates of coronavirus disease 2019 (COVID-19) vaccine hesitancy among PWID in the US-Mexico border region, of whom only 7.6% had received ≥ 1 COVID-19 vaccine dose by September 2021.MethodsBetween October 2020 and September 2021, participants aged ≥ 18 years from San Diego, California, USA, and Tijuana, Baja California, Mexico, who injected drugs within the last month completed surveys and SARS-CoV-2, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) serologic testing. Logistic regressions with robust standard error estimation via generalized estimating equations identified factors associated with being unsure or unwilling to receive COVID-19 vaccines.ResultsOf 393 participants, 266 (67.7%) were willing to receive COVID-19 vaccines and 127 (32.3%) were hesitant (23.4% unwilling and 8.9% unsure). Older participants, those with greater food insecurity, and those with greater concern about acquiring SARS-CoV-2 were more willing to be vaccinated. Higher numbers of chronic health conditions, having access to a smart phone or computer, and citing social media as one's most important source of COVID-19 information were independently associated with vaccine hesitancy. COVID-19-related disinformation was independently associated with vaccine hesitancy (adjusted odds ratio: 1.51 per additional conspiracy theory endorsed; 95% confidence interval: 1.31-1.74).ConclusionsNearly one third of people injecting drugs in the US-Mexico border region were COVID-19 vaccine hesitant, which was significantly associated with exposure to social media, disinformation and co-morbidities and inversely associated with food security and high perceived threat of COVID-19. Interventions that improve accurate knowledge of and trust in COVID-19 vaccines are needed in this vulnerable population.