This retrospective cross-sectional study aimed to evaluate the factors associated with nipple lesion development in puerperae. Analyses were performed using the Poisson regression with robust variance. The level of significance was set at 5% ( p < 0.05). We evaluated 1270 puerperae, among whom 193 (15.4%) presented with nipple lesions. The condition was more prevalent among the mothers who did not receive information about breastfeeding [PR, 1.69; 95% confidence interval (CI), 1.19–2.42], those who underwent cesarean delivery (PR, 1.48; 95% CI, 1.02–2.16), those who used a pacifier (prevalence ratios (PR), 2.04; 95% CI, 1.05–3.95), those who used baby formula only (PR, 1.61; 95% CI, 4.82–5.36) and those who used baby formula combined with breastfeeding (PR, 1.61; 95% CI, 1.06–2.45). A lower incidence of nipple lesions was observed among those who did not receive information on hand expression of breast milk (PR, 0.65; 95% CI, 0.46–0.93) and those who did not breastfeed in the first hour of life (PR, 0.61; 95% CI, 0.38–0.97).