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The aim of this study was to determine the (1) proportion of screened postpartum depression (PPD)–positive mothers, (2) associated risk factors, and (3) impact of PPD screening in a pediatric emergency department (PED).We performed a pilot cohort study using a convenience sample of mothers (n = 209, all ages) of infant patients 6 months or younger presenting to a PED. Mothers completed a computerized survey that included the Edinburgh Postnatal Depression Scale. We assessed frequency of positive screens and performed multivariable logistic regression to identify associated risk factors. We assessed maternal attitudes toward screening at enrollment and 1-month follow-up with positive-screen mothers. Differences in ED utilization were measured.Fifty-seven of 209 mothers (27%; 95% confidence interval [CI], 21%–33%) screened positive for PPD, with 14 (7%) reporting suicidal thoughts. Forty-seven percent (97/209) had never previously been screened, including 58% (33/57) of PPD screen–positive mothers. Current unemployment status (adjusted odds ratio [aOR], 2.76; 95% CI, 1.25–6.13) and first-time motherhood (aOR, 3.92; 95% CI, 1.72–8.91) were associated with a positive screen. At 1-month follow-up, mothers (35/37) reported PED-based PPD screening was important. After adjustment for sociodemographic factors, PPD screen–positive mothers had increased PED utilization (aOR, 1.29; 95% CI, 1.03–1.61).Approximately 1 in 4 mothers screened positive for PPD in a PED, with almost 1 in 10 reporting suicidal thoughts. The majority of PPD screen–positive mothers had not been screened previously. Our study helps to inform future efforts for interventions to support mothers of young infants who use the PED for care.