The objective of this study was to examine whether duration of exclusive breastfeeding is associated with elevated weight gain in infants during the first two years of life. In this prospective cohort study 2624 healthy term neonates were followed from birth to age 2 years in 4 German study centres. Data on breastfeeding and potential confounders were gathered by questionnaires. Data on anthropometric measures at birth and age 2 years were obtained from routine standardised medical check up documentation. Odds ratios for the association between breastfeeding and weight gain until age 2 years (> or = 90th sex-specific percentile of the cohort) were calculated by logistic regression, adjusting for age at introduction and composition of solid food, maternal BMI, maternal smoking during pregnancy, socioeconomic status, study centre, birth order and, in unstratified analysis, sex. Children exclusively breastfed for less than 6 months had a greater risk of elevated weight gain at the age of 2 years than children breastfed for 6 months and more (OR (95% CI): 1.65 (1.17, 2.30)). Duration of exclusive breastfeeding was inversely associated with the risk of elevated weight gain in a strongly duration-dependent way. Those infants who were exclusively breastfed 1 month at the most had twice as often elevated weight gain (OR (95% CI): 1.99 (1.34, 2.97)) compared to infants breastfed at least 6 months. Our data show that exclusive breastfeeding protects against elevated weight gain during infancy which may be the first step on the pathway of obesity development.