Exclusive breastfeeding is the best form of nutrition for infants in the first 6 months of life. The aim of this study was to determine the prevalence of exclusive breastfeeding in Tehran, Islamic Republic of Iran in the first 6 months of life, and the factors that influence it. In a population-based, cross-sectional study 538 mothers with children aged 6–24 months completed an interview questionnaire. Only 46.5% of mothers exclusively breastfed their infant in the first 6 months of life. In multivariate analysis formula supplementation in the hospital (OR = 0.41, 95% CI 0.17–0.95) and mother receiving conflicting infant feeding advice (OR = 0.53, 95% CI 0.37–0.78) had a negative effect on exclusive breastfeeding. Mother’s intention to exclusively breastfeed (OR = 5.85, 95% CI 2.88–11.9) and infant having first breast contact 6–30 minutes after delivery (OR = 2.35, 95% CI 1.17–4.72) had positive effects on exclusive breastfeeding.