This study examines trends of injection drug users' (IDUs) utilization of a Philadelphia, Pennsylvania, syringe exchange program (SEP) from 1999 to 2014, with a focus on demographic changes and geographic shifts. Methods: Prevention Point Philadelphia's SEP registration data were analyzed using linear regression, Pearson's chi-square, and t-tests for 1999, 2005, 2009, and 2014. Differences across the four years were tested, as were pair-wise differences. Results: Over time new SEP registrants have become younger, more racially diverse, and geographically more concentrated in specific areas of the city, corresponding to urban demographic shifts. The percent change of new syringe registrants by zip code of residence identifies West Philadelphia and Northwest Philadelphia as having experienced substantial growth from 2009 to 2014. Overall, the number of new registrants per year has decreased, however the number of syringes exchanged has increased. Conclusions: Gentrification, cultural norms, and changes in risk perception are believed to have contributed to the changes in SEP registration. Having a more informed understanding of who the current users of syringe exchange are, where they are located, and the recent trends in their patterns of use, is necessary for making future policy decisions in order to sustain decreases in HIV and HCV transmission. It will thus be important for SEPs to adapt to the new face of the “typical” IDU by re-thinking placement of exchanges, outreach strategies, staff abilities to work with more diverse users, how risk of disease is communicated, and how these changes might impact the types of services needed.