We evaluated the effect of syringe acquisition on syringe disposal among HIV-positive injection drug users (IDUs) in Baltimore, New York City, and San Francisco (N = 680; mean age 42 years, 62% male, 59% African-American, 21% Hispanic, 12% White). Independent predictors of safe disposal were acquiring syringes through a safe source and ever visiting a syringe exchange program. Weaker predictors included living in San Francisco, living in the area longer, less frequent binge drinking, injecting with an HIV+ partner, peer norms supporting safe injection, and self-empowerment. Independent predictors of safe "handling"-both acquiring and disposing of syringes safely-also included being from New York and being older. HIV-positive IDUs who obtain syringes from a safe source are more likely to safely dispose; peer norms contribute to both acquisition and disposal. Interventions to improve disposal should include expanding sites of safe syringe acquisition while enhancing disposal messages, alternatives, and convenience.