Little published information exists to guide health care institutions in establishing syringe exchange program (SEP) services. To address this gap, this article discusses organizational issues encountered in the implementation of a hospital-based SEP in San Francisco, California (USA). Investigators collaborated with a community organization in implementing a county hospital-based SEP. SEP services integrated into a public hospital presented unique challenges directly related to their status as a health care institution. In the course of introducing SEP services into a hospital setting as part of a clinical trial, various ethical, legal, and logistical issues were raised. Based on these experiences, this paper provides guidance on how to integrate an SEP into a traditional health care institution.