Drotrecogin alfa was introduced in 2001 as a treatment for severe sepsis following the results of the PROWESS trial; however, in October of 2011 drotrecogin alfa was re moved worldwide due to a lack of survival benefit demonstrated in the PROWESS-SHOCK trial. There is limited literature describing the outcomes seen outside of the controlled research environment with drotrecogin alfa. Objective: The purpose of this study was to describe the outcomes of patients treated with drotrecogin alfa in clinical practice at an urban safety net hospital. Methods: A retrospective analysis was conducted on all patients that received drotrecogin alfa from January 2002 to April 2008. The primary outcome was 28-day mortality in all patients. Baseline patient characteristics and 28-day mortality were compared to those found in the PROWESS trial. Results: In the current study, 59.5% expired before 28 days which was significantly higher than the 24.7% mortality rate found in PROWESS (p < 0.0001). However, patients in the current study were more ill than those found in PROWESS as shown by the average APACHE II score in the current study being 28.2 versus 24.6 in PROWESS (p < 0.0001). Patients with HIV had the highest 28-day mortality rate of 77% while patients that were obese had the lowest 28-day mortality rate of 33.3%. Conclusions: Patients treated with drotrecogin alfa in clinical practice tended to have a higher mortality rate than those patients treated in the PROWESS study. However, patients in the current study tended to be more ill than those in PROWESS.