This study was conducted to compare needle and syringe sharing practices among injecting drug users (IDUs) in two neighborhoods, one with and one without a needle and syringe program (NSP). In 2005, 419 street-based IDUs were interviewed at specific locations in two neighborhoods where IDUs are known to congregate. We compared self-reported needle and syringe access and use between IDUs from a neighborhood with an active NSP to IDUs from a neighborhood without such an intervention. A significantly smaller proportion of IDUs from the former neighborhood reported having used a shared needle/syringe over a 1-month period (21.0%) compared to IDUs from the latter neighborhood (39.9%; adjusted odds ratio, 0.24; 95% confidence interval, 0.13-0.45). These findings indicate that access to an NSP may reduce needle and syringe sharing practices. Therefore, these programs should be intensified in settings with concentrated HIV epidemics among IDUs in Iran.