Background: Taiwan has a growing HIV/AIDS epidemic that has recently shifted to an increase among injection drug users (IDUs). This study aimed to measure the prevalence and incidence and identify the correlates of HIV infection among IDUs in a large methadone maintenance treatment program (MMTP) in Taipei, Taiwan. Methods: Data from intake interviews and HIV testing completed by IDUs upon admission to the Taipei City Hospital MMTP in 2007–2010 were included in this analysis. HIV testing was repeated semi-annually among maintained clients who were HIV-negative during MMTP admission. Results: Of 1444 IDUs admitted, 85.9% were male, median age was 40 years, and mean years of injecting was 14.3 (range: 1–64). The prevalence of HIV, HCV, and HIV/HCV co-infection was 13.4%, 91.1%, and 13.2%, respectively. In multivariable analysis, HIV infection was associated with sharing syringes during the 6 months prior to admission (OR = 14.76, 95% CI 10.31–21.13), homelessness (OR = 6.46, 95% CI 1.49–28.00), and lifetime number of MMTP admissions (OR = 1.76, 95% CI 1.30–2.38) and times incarcerated (OR = 1.10, 95% CI 1.03–1.18). HIV seroincidence was 1.15/100 person-years at risk (95% CI .62–8.77/100 PY) among IDUs who were HIV-negative at first admission. Conclusions: Taiwanese IDUs in MMTP have a high HIV prevalence, which was associated with syringe sharing and other factors related to social marginalization. Our findings highlight the importance of harm reduction programs, including syringe exchange, along with HIV-prevention education.