Tobacco use is the largest preventable cause of death in the United States. Associations between cigarette smoking and HIV risk behaviors were examined among 669 injection drug users (IDU) in the 2006 wave of the National HIV Behavioral Surveillance System in Baltimore, Maryland, using respondent-driven sampling. The adjusted prevalence of smoking among IDU was 92.1%, with 32.7% smoking < 1 pack of cigarettes per day (light smoking) and 59.3% smoking ≥ 1 packs per day (heavy smoking). Self-reported HIV prevalence decreased as smoking frequency increased (p = 0.001). In multivariate analysis, heavy smokers were more likely to report painkiller use and binge drinking and less likely to report anal sex or health care use in the past year than light smokers. Results suggest that health care use mediates the relationship between heavy smoking and self-reported HIV. Integrating smoking cessation with HIV prevention services could address unmet health needs in IDU.