Aim: The aim of this prospective study was to examine the relationship between success of exclusive breastfeeding and postpartum depressive symptomatology. Our hypothesis was that mothers with depressive symptoms initially fail exclusive breastfeeding. Subjects and Methods: One hundred ninety-seven mothers were enrolled in the study. The participants were interviewed twice. The first visit was within the first 48 hours after birth. The Edinburgh Postnatal Depression Scale (EPDS) was completed by the participants. The second interview was performed at 6 weeks. Participants answered questions regarding methods of breastfeeding for 6 weeks, any methodological problems, and nipple pain. The EPDS was again completed by the participants at 6 weeks. All newborns were term infants. Results: All the participants were divided into two groups: exclusive breastfeeding and mixed-feeding (partial breastfeeding and/or bottle feeding). Both groups were compared in terms of features, such as mode of delivery, parity, prevalence of depressive symptomatology (at 48 hours and 6 weeks), and delayed onset of lactation within the first 48 hours. Statistical significance was found for only three variables: delayed onset of lactation within the first 48 hours, gestational age, and the problems related to breastfeeding methods. Conclusions: Clinicians should pay special attention to any lactation difficulty during the first week postpartum. Early lactation difficulties are associated with greater risk of early termination of breastfeeding and lower breastfeeding success. © Mary Ann Liebert, Inc.