Background: Overall progress in getting to zero new HIV infections in San Francisco has been made since 2012. However, among people who inject drugs (PWID), there has been no clear downward trend in new HIV infections in recent years. Direct measures of the rate of HIV acquisition and characterization of factors associated with higher rates among PWID are needed to help achieve HIV elimination. Methods: This study is a secondary analysis of the National HIV Behavioral Surveillance survey of PWID in San Francisco in 2022. HIV incidence is estimated using age of first injection drug use and date of first HIV-positive test or interview date as the exposure period. Factors associated with HIV seroconversion were identified by Cox regression. Results: Of 518 PWID, 12 newly tested HIV positive in the survey and 38 reported a prior positive test. HIV incidence was calculated as 0.46 per 100 person-years (95% confidence interval [CI]: 0.35 to 0.61). HIV incidence rates were significantly higher among PWID who were men who have sex with men (adjusted hazard ratio [aHR] 15.98, 95% Cl 7.77 to 32.87, P < 0.001), transgender (aHR 8.64, 95% Cl 2.76 to 27.08, P < 0.001), and Hispanic (aHR 2.85, 95% Cl 1.23 to 6.63, P < 0.001). Conclusions: We found a moderate HIV incidence of ∼5 per 1000 person-years among PWID in San Francisco, with significantly higher rates among sexual, gender, and ethnic minority groups of PWID. Further progress in getting to zero new HIV infections will require more vigorous scale-up of effective prevention interventions, such as PrEP, specifically reaching vulnerable groups of PWID.