IMPORTANCE: Readmission penalties have catalyzed efforts to improve care transitions, but few programs have incorporated viewpoints of patients and health care professionals to determine readmission preventability or to prioritize opportunities for care improvement. OBJECTIVES: To determine preventability of readmissions and to use these estimates to prioritize areas for improvement. DESIGN, SETTING, AND PARTICIPANTS: An observational studywas conducted of 1000 general medicine patients readmitted within 30 days of discharge to 12 US academic medical centers between April 1, 2012, and March 31, 2013.We surveyed patients and physicians, reviewed documentation, and performed 2-physician case review to determine preventability of and factors contributing to readmission.We used bivariable statistics to compare preventable and nonpreventable readmissions, multivariable models to identify factors associated with potential preventability, and baseline risk factor prevalence and adjusted odds ratios (aORs) to determine the proportion of readmissions affected by individual risk factors. MAIN OUTCOME AND MEASURE: Likelihood that a readmission could have been prevented. RESULTS: The study cohort comprised 1000 patients (median age was 55 years). Of these, 269 (26.9%) were considered potentially preventable. In multivariable models, factors most strongly associated with potential preventability included emergency department decision making regarding the readmission (aOR, 9.13; 95%CI, 5.23-15.95), failure to relay important information to outpatient health care professionals (aOR, 4.19; 95%CI, 2.17-8.09), discharge of patients too soon (aOR, 3.88; 95%CI, 2.44-6.17), and lack of discussions about care goals among patients with serious illnesses (aOR, 3.84; 95%CI, 1.39-10.64). The most common factors associated with potentially preventable readmissions included emergency department decision making (affecting 9.0%; 95%CI, 7.1%-10.3%), inability to keep appointments after discharge (affecting 8.3%; 95%CI, 4.1%-12.0%), premature discharge from the hospital (affecting 8.7%; 95%CI, 5.8%-11.3%), and patient lack of awareness of whom to contact after discharge (affecting 6.2%; 95%CI, 3.5%-8.7%). CONCLUSIONS AND RELEVANCE: Approximately one-quarter of readmissions are potentially preventable when assessed using multiple perspectives. High-priority areas for improvement efforts include improved communication among health care teams and between health care professionals and patients, greater attention to patients' readiness for discharge, enhanced disease monitoring, and better support for patient self-management.