To evaluate the use of hydrogel dressings for the prevention and treatment of nipple soreness in lactating women as compared with the common intervention of lanolin ointment. The hypothesis was as follows: Participants using hydrogel dressings as a preventive measure for nipple soreness will experience greater pain relief and a lower rate of nipple wounds as compared with the control group. The secondary hypothesis was that the reduction of nipple soreness in the treatment group would produce a longer duration of breastfeeding as compared with the control group. A multicentered, prospective, randomized controlled clinical trial evaluating a sample of 106 lactating mothers. Study sites were the University of Alabama Medical Center at Birmingham (an inner-city teaching hospital) and Northeast Health System (a community hospital in Beverly, Massachusetts). Participants were older than age 18, fluent in English, and had an operational telephone in the residence. Other inclusion criteria were singleton, vaginal deliveries; no prior breastfeeding experience; and written informed consent. Participants were randomized to either the lanolin ointment or the hydrogel dressings group and received instructions specific to their assignment. All participants received breastfeeding education provided by a board-certified lactation consultant. During the initial 12 study days, participants identified pain intensity using a numeric pain intensity scale and verbal descriptor scale. Subjective data were collected via self-reported skin assessments of the bilateral breasts, nipples, and areolae. Breastfeeding duration was established by a follow-up telephone call at 2 months. The hydrogel dressings group had significantly greater reduction in pain score mean values at baseline, on study Day 10, and on study Day 12 in comparison to the control group. Participants using the hydrogel dressings discontinued treatment sooner than participants in the lanolin ointment group. The lanolin ointment group had eight breast infections, whereas the hydrogel dressings group had none. Hydrogel dressings are a safe, available treatment that provided more effective pain management for nipple soreness than the common intervention of lanolin ointment.