Regulations to reduce housestaff work hours were implemented in part to improve patient safety. Although extended shifts were associated with self-reported attentional failures in one study, other research has not found an association between errors and number of hours worked (but demonstrated a relationship between overall work stress and self-reported errors). To assess for depression or burnout, this prospective study surveyed pediatric residents and correlated these findings with data on medication errors committed by the same residents. Nearly one quarter of residents were found to be at high risk of major depression, and the rate of medication errors was significantly higher in these residents, although burnout was not correlated with errors. This study adds to a growing body of research suggesting that emotional stressors as well as work hours affect the safety of care provided by housestaff.