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This longitudinal, descriptive study described the level of depressive symptoms in mothers of preterm infants from birth through 27 months corrected age and examined factors associated with depressive symptoms. The framework for the study was guided by an ecological developmental systems perspective and an adaptation of the Preterm Parental Distress Model.In this model, we hypothesize that a mother's emotional distress to the birth and parenting of a prematurely born child is influenced by personal and family factors, severity of the infant's health status, and illness-related stress and worry. Participants were 102 mothers of preterm infants who were off the ventilator and not otherwise dependent on major technology at enrollment.Mean depressive symptoms scores on the Center for Epidemiologic Studies Depression Scale (CES-D) during hospitalization were high and more than half the mothers (63%) had scores of ≥16 indicating risk of depression. Depressive scores declined over time until 6 months and then were fairly stable. Unmarried mothers, mothers of infants who were rehospitalized, and mothers who reported more maternal role alteration stress during hospitalization and worry about the child's health had more depressive symptoms through the first year. Mothers who reported more parental role alteration stress during hospitalization (odds ratio [OR] = 1.570, 95% confidence interval [CI]: 1.171–2.104) and more worry about the child's health (OR = 2.350, 95% CI: 1.842–2.998) were more likely to experience elevated CES-D scores that put them at risk of depression. Also, mothers of rehospitalized infants had decreasing odds of elevated CES-D scores over time (OR = 0.982 per week, 95% CI: 0.968–0.996).Findings have implications for the support of mothers during hospitalization and in the early years of parenting a preterm infant.