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To identify and model the effects of sleep loss and fatigue on resident–physicians’ professional lives and personal well-being.In 2001–02, 149 residents at five U.S. academic health centers and from six specialties (obstetrics–gynecology, emergency medicine, family medicine, internal medicine, pediatrics, surgery) were recruited for the study. Residents were all in good standing in their programs. In a mixed-methods design, focus groups consisted of an average of seven (range, three to 14) individuals in the same year of training and residency program, for a total of 60 interns and 89 senior residents. Trained moderators conducted focus groups using a standardized, semistructured discussion guide. Participants also completed a 30-item quantitative questionnaire assessing sleepiness and workplace sleep attitudes that included the Epworth Sleepiness Scale (ESS).Residents described multiple adverse effects of sleep loss and fatigue on learning and cognition; job performance, including professionalism and task performance; and personal life, including personal well-being and relationships with spouse or significant other and family. Only 16% of the sample scored within the “normal” range on the ESS; 84% scored in the range for which clinical intervention is indicated. Sleepiness was consistent across institution, specialty, years of training, age, gender, marital status, and having children.More residents perceived that sleep loss and fatigue had major impact on their personal lives during residency, leaving many personal and social activities and meaningful personal pleasures deferred or postponed. Sleep loss and fatigue also had major impact on residents’ abilities to perform their work. This finding further substantiates the growing concern about the potential impact on professional development. These observations should be taken into account in developing new training guidelines and educational interventions for housestaff.