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Many factors may influence a woman’s decision to start and maintain breastfeeding.This study aimed to investigate the factors associated with breastfeeding cessation in twin infants during the first 6 months after birth and to describe the main reasons for weaning cited by mothers of twins.This is a secondary data analysis of a prospective randomized trial conducted in Brazil. Data were obtained through longitudinal quantitative and qualitative self-reported interviews. One hundred twenty-eight women pregnant with twins and their 256 infants were followed for up to approximately 6 months, during which time breastfeeding data were obtained through face-to-face interviews at three different points after birth: 30 to 40 days (Time 1), 90 days (Time 2), and 180 days (Time 3). The association between weaning and the investigated factors was examined using survival analysis methodologies.Nonexclusive breastfeeding (p = .004, Cox proportional hazards regression model), a lack of support during the lactation period (p = .001), difficulty breastfeeding (p = .003), a breastfeeding duration shorter than 12 months in a previous pregnancy (p = .001), and infants’ birth weight less than 2,300 g (p < .001) were the factors associated with breastfeeding cessation. The main reasons for weaning cited by mothers of twins were insufficient human milk supply, infants’ behavior, and returning to work.We have identified the factors associated with weaning in twin infants during the first 180 days of life. This knowledge can help improve strategies to increase breastfeeding rates in twins.