Objectives: In an effort to reduce HIV transmission among injection drug users (IDUs), New York State deregulated pharmacy syringe sales in 2001 through the Expanded Syringe Access Program by removing the requirement of a prescription. With evidence suggesting pharmacists' ability to expand their public health role, a structural, pharmacy-based intervention was implemented to determine whether expanding pharmacy practice to include provision of HIV risk reduction and social/medical services information during the syringe sale would (a) improve pharmacy staff attitudes toward IDUs (b) increase IDU syringe customers, and (c) increase prescription customer base in New York City neighborhoods with high burden of HIV and illegal drug activity. Methods: Pharmacies (n = 88) were randomized into intervention (recruited IDU syringe customers into the study and delivered intervention activities), primary control (recruited IDU syringe customers only) and secondary control (did not recruit IDUs or deliver intervention activities) arms. Results: Pharmacy staff in the intervention versus secondary control pharmacies showed significant decreases in the belief that selling syringes to IDUs causes community loitering. Conclusions: Structural interventions may be optimal approaches for changing normative attitudes about highly stigmatized populations.