The research presented in this paper details the results of an assessment of the risk factors associated with having a positive syphilis or HIV serology. The study was conducted using a sample of not-in-treatment drug users volunteering to participate in an HIV risk reduction intervention. The sample was composed of individuals who had injected drugs within 30 days or smoked crack cocaine 48 hours prior to participation in the study. Study participants were approximately 75% male and 66% African-American. All participants provided a blood sample to be tested for HIV and syphilis. Analysis of risk was conducted using univariate and multivariate statistical methods. Multivariate analysis of blood results showed that women, African-Americans, and those having a positive blood test for HIV were at higher odds of having a positive syphilis test. Analysis also showed that being a gay or bisexual male, having a history of drug injection, having less than a high-school education, having a history of trading sex for money, being African-American, and having a positive blood test for syphilis significantly increased the odds of a positive HIV test. Implications for HIV and STD prevention are discussed.