Abstract Objectives: This is a single-arm prospective longitudinal clinical trial investigating the feasibility of using a non-hormonal hyaluronic acid (HLA) vaginal gel (Hydeal-D) to improve estrogen deprivation vaginal health symptoms in postmenopausal women with a history of hormone receptor-positive cancer. Methods: Preliminary data from an ongoing clinical trial were examined. Demographics, medical information, and clinical assessment from breast cancer patients enrolled on study at baseline (n=23) and at 4-6 weeks (n=18) are presented. Eligible participants included those with a history of breast cancer receiving treatment with an aromatase inhibitor (AI) at the time of enrollment. Furthermore, participants could not have evidence of disease and had to have completed treatment for at least 3 months and no longer than 5 years (excluding AIs). Study participants were instructed to use HLA daily for 2 weeks, then 3 times per week for 12-14 weeks. Study outcomes include: pelvic exam results as recorded on a clinician evaluation form with the Vaginal Assessment Scale (VAS); patient-reported outcomes (PROs) of the Sexual Activity Questionnaire (SAQ), Sexual Self-Schema Scale, and Female Sexual Function Index (FSFI); PROMIS sexual function items; and exploratory items. Results: The mean age was 56 years (range, 42-75). Seventy-four percent (17/23) were married or living with a partner. Fifty-seven percent (13/23) reported sexual activity with a partner at baseline, which was 72% (13/18) at 4-6 weeks. On the VAS, 65% (15/23) reported symptoms of severe dryness at baseline and 61% (14/23) reported severe dyspareunia; these reported symptoms decreased to 6% (1/18) and 6% (1/18), respectively, at 4-6 weeks. Vaginal pH scores were greater than 6.5 in 30% (7/23) at baseline; by 4-6 weeks, only 22% (4/18) had a pH in this elevated range. At baseline, 78% (18/23) had minimal moisture and 22% (5/23) had no vaginal moisture seen on exam; by 4-6 weeks, 11% (2/18) had normal moisture and 89% (16/18) had minimal moisture. Pain with pelvic exams declined over time—87% (20/23) had pain at baseline, with 22% (5/23) rating it as severe, and 78% (14/18) had pain at 4-6 weeks, with none of the women rating their pain as severe. Forty-eight percent (11/23) indicated confidence about future sexual activity at baseline, which was 56% (10/18) at 4-6 weeks. Level of concern about sexual/vaginal health was measured on a scale of 0-10, with greatest concern rated as a 9 or 10. Sixty-one percent (14/23) of the women fell into this range at baseline; the percentage decreased to 28% (5/18) at 4-6 weeks. Conclusions: Preliminary findings suggest that an HLA vaginal gel may improve vaginal/sexual health issues and concerns of breast cancer survivors both in their perceived symptoms and on clinical exam; however, further study is needed to examine if these promising trends continue over time and to determine the ideal frequency of product administration. Citation Format: Carter J, Seidel B, Stabile C, Dickler M, Goldfrank D, Baser R, Goldfarb S. Feasibility of a non-hormonal vaginal moisturizer in postmenopausal cancer survivors. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-06.