Objective. To identify stress and stress-relieving mechanisms among second-year pharmacy students in a 3-year doctor of pharmacy (PharmD) program using a Mastery Learning Educational Model and to compare findings with those from a 4-year program. Methods. Second-year PharmD students in a 3-year program were asked to complete a series of questionnaires including the Perceived Stress Scale (PSS) regarding stress and stress-relieving activities.Results. The average PSS score for the 3-year PharmD cohort was significantly higher than the score of demographically similar students enrolled in a 4-year PharmD program (P 5 0.04). There were significant differences between the 2 groups' scores on 5 items on the PSS including how often they: were upset because something happened unexpectedly, felt unable to control important things, felt nervous and stressed, thought about things that had to be accomplished, and were able to control the way they spent their time. The rate of prescription drug misuse among those in the 3-year PharmD program was 11.6%. Conclusions. Students in a 3-year PharmD program with a unique educational model experienced more stress than students in a traditional 4-year PharmD program.