Sore and cracked nipples are common and may represent an obstacle to successful breastfeeding. In Italy, it is customary for health professionals to prescribe some type of ointment to prevent or treat sore and cracked nipples. The efficacy of these ointments is insufficiently documented. The incidence of sore and cracked nipples was compared between mothers given routine nipple care, including an ointment (control group), and mothers instructed to avoid the use of nipple creams and other products (intervention group). Breastfeeding duration was also compared between the two groups. Eligible mothers were randomly assigned, after informed consent, to one of the two groups. No difference was found between the control (n = 96) and the intervention group (n = 123) in the incidence of sore and cracked nipples and in breastfeeding duration. However, several factors were associated with sore nipples and with breastfeeding duration. The use of a pacifier and of a feeding bottle in the hospital were both associated with sore nipples at discharge (p = 0.02 and p = 0.03, respectively). Full breastfeeding up to 4 months postpartum was significantly associated with the following early practices: breastfeeding on demand, rooming-in at least 20 hours/day, non-use of formula and pacifier, no test-weighing at each breastfeed. The incidence of sore and cracked nipples and the duration of breastfeeding were not influenced by the use of a nipple ointment. Other interventions, such as providing the mother with guidance and support on positioning and latching, and modifications of hospital practices may be more effective in reducing nipple problems.