Reducing readmissions is a patient safety priority. Project Re-Engineered Discharge (RED) was an AHRQ-funded randomized trial that successfully reduced readmissions and has been replicated with mixed results in other hospitals. This qualitative study used participant observation, focus groups, and individual interviews to characterize factors that affected the implementation of RED at five hospitals in California. Investigators found that leadership commitment, a strong safety culture, and fidelity to Project RED's original design were associated with successfully implementing and sustaining the initiative. Two sites did not sustain the project because they lacked these factors. This study demonstrates that evidence-based safety initiatives may vary in their effectiveness depending on how they are implemented.