We examined the prevalence and correlates of HIV-related sexual risk and substance use behaviors among Asian Pacific Islander (API) male-to-female (MTF) transgendered individuals, referred to here as API transgendered women. As part of a larger study on HIV risk among transgendered women of color (Nemoto, Operario, Keatley, Han, & Soma, 2004), a sample of 110 API transgendered women in San Francisco completed individual interviews, of which 13% reported being HIV-positive. In the past 30 days, one fifth of the sample engaged in unprotected receptive anal intercourse (URAI) with any male partner, nearly one half had sex while under the influence of substances, and over half used illicit drugs. In multivariate models, URAI was associated with commercial sex work (odds ratio [OR] = 4.23, 95% confidence interval [CI] = 1.10, 16.25) and previous attempted suicide (OR = 5.83, 95% CI = 1.02, 33.44). Sex under the influence of substances was associated with commercial sex work (OR = 3.35, 95% CI = 1.11, 10.13) and having a college degree (OR = 5.32, 95% CI = 1.34, 21.18). Illicit drug use was associated with commercial sex work (OR = 7.15, 95% = 2.26, 22.63). Findings suggest that API MTF transgenders are on the front line of HIV risk for the API community, and provide insight into factors within this group that might contribute to unsafe sex and substance use.