To compare aliposomal gel with and without chamomile extract for the prevention of radiation dermatitis in breast cancer patients undergoing radiotherapy. This study was adouble-blind randomized clinical trial. Atotal of 100 participants undergoing radiotherapy for breast cancer were recruited. The primary outcome was the occurrence of dry desquamation. Cumulative dose of ionizing radiation at the first occurrence of dry desquamation, occurrence of erythema, moist desquamation, global radiation dermatitis, and any signs and symptoms self-reported by participants were secondary outcomes. Dry desquamation occurred in 6.0% of the participants using chamomile liposomal gel and 12.2% of those using liposomal gel (p = 0.32). The mean cumulative dose of ionizing radiation for the first occurrence of dry desquamation was 45.1 Gy in the chamomile liposomal gel group and 43.7 Gy in the liposomal gel group. There were no differences between the two gels in the occurrence of erythema, dry desquamation, moist desquamation, and radiation dermatitis compared to liposomal gel. There was alower proportion of reported symptoms in the chamomile liposomal gel group compared to liposomal gel group in the first 3weeks of radiation, especially for itching (p = 0.05). No statistically significant differences between the two gels were found in radiation dermatitis occurrence and dose at first occurrence. Comparing to the literature, it seems that both interventions may be effective, which might explain the lack of statistical difference between the groups.