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We examined how house officers coped with serious medical mistakes to gain insight into how medical educators should handle these situations. An anonymous questionnaire was mailed to 254 house officers in internal medicine asking them to describe their most important mistake and their response to it; 45% (N = 114) reported a mistake and completed the questionnaire. House officers experienced considerable emotional distress in response to their mistakes and used a variety of strategies to cope. In multivariate analysis, those who coped by accepting responsibility were more likely to make constructive changes in practice, but to experience more emotional distress. House officers who coped by escape-avoidance were more likely to report defensive changes in practice. For house officers who have made a mistake, we suggest that medical educators provide specific advice about preventing a recurrence of the mistake, provide emotional support, and help them understand that distress is an expected concomitant of learning from the experience.