OBJECTIVE: As the cornerstone of any health system, hospitals have a crucial role in response to disasters. Because hospital experiences in disaster response can be instructive, this study examined the challenges of hospital response to the twin earthquakes of 2012 in East Azerbaijan, Iran. METHODS: In this qualitative study, the challenges of hospital response in the East Azerbaijan earthquakes were examined through focus group discussions. Participants were selected purposefully, and focus group discussions continued until data saturation. The data were manually analyzed by using Strauss and Corbin's recommended method. RESULTS: Hospitals were faced with 6 major challenges: lack of preparedness, lack of coordination, logistic deficiencies, patient/injured management, communication management, and other smaller challenges that were categorized in the "other challenges" category. The main theme was the lack of preparedness for disasters. CONCLUSION: Although hospital preparedness is emphasized in credible references, this study showed that lack of preparedness is a major challenge for hospitals during disasters. Thus, it seems that hospital officials' disaster risk perception and hospital preparedness should be improved. In addition, hospital preparedness assessment indexes should be included in the hospital accreditation process. (Disaster Med Public Health Preparedness. 2017;11:422-430).