Abstract Aim: To compare the effectiveness for radiodermatitis prophylaxis of Fusidic acid and Betamethasone valerate containing cream, pure vaselin and emollient dermocosmetic cream during radiotherapy for breast cancer. Method: We prescribed one of the 3 different creams per patient respectively at the start date of breast cancer radiotherapy (conventional radiotherapy: CRT, 50 Gy in 2 Gy/fraction plus a 10 Gy boost for a total of 60 Gy; or hypofractionated radiotherapy: HRT, 40 Gy in 2.67 Gy/fraction plus a 10 Gy Boost for a total of 50 Gy) at our clinic and instructed them to use the cream daily after each fraction throughout the whole treatment. Weekly photographs of the thorax, including the treated breast anteriorly and laterally, were taken with the onset of treatment, where a gray card setting for color balance standardization was performed. The weekly skin changes were recorded prospectively and assessed retrospectively according to the RTOG radiodermatitis side effect scale. A total of 64 cases have been enrolled in the study till now and 54 out of 58 cases who completed their radiotherapy were evaluated for the current analysis (photographs flawed in three, one refused her photographs to be included in the study). The photographs were processed for color matching with the gray card set using the Adobe Reader Photoshop CC software via the red color histogram and the pre- & post-radiotherapy skin redness were objectively compared via the histogram. The data were analyzed using SPSS, version 23. Results: The treatment was conventional in 25 patients and hypofractionated in 29 patients. Grade 2 radiodermatitis was seen in 37% of the cases at the end of treatment. The color scale final grade 2 radiodermatitis rate was 29.6% (16 cases), consistent with the clinical findings. The cream used was emollient dermocosmetic in 17 (31.5%, CRT 10, HRT 7), fusidic acid and betamethasone valerate in 19 (35.2%, CRT 13, HRT 6), and pure vaseline in 18 (33.3%, CRT 6, HRT 12) cases. There were 4 grade 1 RD in first week, 15 grade 1 RD in second week, 29 grade 1 and 1 grade 2 RD in the third week. The grade 2 RD rate increased to 16.7% (n: 9) in the fourth week. As lower red density values in the red scale representing increased erythema, the pre-radiotherapy breast median value of 230 (range: 166-256) decreased to a median value of 209.5 (range: 114-252) at the end of radiotherapy with a median change of 14%, not significantly different with creams (p=0.06) or with fractionation (p>0.05). Conclusion: Grade 2 acute radiodermatitis wasless commonly encountered with prophylactic creams in our cohort while no significant difference could be defined between creams and fractionation used. Digital follow up of the protocol patients is currently continuing to be documented for future reporting. Citation Format: Sezen D, Bolukbasi Y, Corak Cebi C, Selek U. Comparison of three different topical agents on prevention of acute radiodermatitis during breast cancer radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-18.