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Background: Short interpregnancy interval (IPI) is associated with risk of adverse pregnancy outcomes; however, few studies have evaluated the role of depression as a risk factor for short IPI. Puerto Rican women in the United States experience disparities in adverse birth outcomes and have the highest birth rates. Methods: We analyzed the association between prenatal depressive symptoms and IPI in Proyecto Buena Salud, a prospective cohort of predominantly Puerto Rican women in Western Massachusetts (2006-2011). Depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) in early, mid, and late pregnancy. We calculated follow-up time as the difference between the date of delivery of the index pregnancy and the last menstrual period of the subsequent pregnancy using medical records and billing data. We defined short IPI as ≤18 months. Results: Of 1262 eligible women, 35% ( n  = 440) had at least probable minor depression (EPDS scores ≥13) and 25% ( n  = 315) had probable major depression (EPDS scores ≥15). Participants were followed for a median of 3.7 years (interquartile range = 1.4-6.0 years) and 240 (20.6%) participants experienced a short IPI. After adjusting for risk factors, women with probable minor depression (adjusted odds ratio [aOR] = 1.39, 95% confidence interval [CI] = 1.02-1.88) and probable major depression (aOR = 1.42, 95% CI = 1.02-1.97) during pregnancy had increased odds of short IPI. Conclusions: Prenatal depressive symptoms were common in this Puerto Rican population and were associated with a modest increase in odds of short IPI. Further examination of the pathways through which mental health may affect IPI in vulnerable populations is warranted.