Introduction: There is a paucity of detailed health related quality of life (HRQoL) outcomes available for women undergoing radical cystectomy (RC). Our primary objective was to evaluate HRQoL after RC using patient reported outcome measures (PROMs) in women to identify patterns of recovery and whether any gender specific differences exist. Methods: We conducted a prospective HRQoL study of patients undergoing RC using 14 different PROMs over a 2 year follow up period to evaluate the pattern of QoL changes from baseline. Using the Wald test, we simultaneously tested whether the sex and sex-urinary diversion interaction coefficients were non-zero to assess whether post-RC QoL was different between males and females. To assess whether post-RC QoL differed by sex, we fit one general estimating equation regression model for each QoL domain. This model estimates the mean QoL over the follow-up period. For each QoL domain, we build a regression model with QoL as the outcome and time point, urinary diversion type, and a time point-diversion type interaction as covariates. Results: We observed statistically significant differences in post-RC QoL between men and women. Domains demonstrating female/male differences included global QoL, physical functioning, social functioning, body image, sexual functioning, mental health, and satisfaction with life. Women reported worse global QoL, physical function, social function, mental health and body image symptoms, including women who received continent diversions. (Figure 1a-c) Most of the observed differences were numerically small and correlate with a minimal clinically significant change. Women reported slightly higher sexual functioning (Figure 1d) and satisfaction with life scores compared to men. Over the recovery period, there were no female/male related differences found for bowel function, fear of recurrence, or decisional conflict. Conclusions: We identified several female specific differences in reported HRQoL after RC compared to men. Most differences were small and of questionable clinical significance; however, much work is needed to better understand the HRQoL specific to women undergoing RC. Characterization of sex-related differences is an essential step to improve preoperative counseling and make meaningful improvements in female patients’ QoL following RC. SOURCE OF Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, the National Cancer Institute Cancer Center Core grant number P30-CA008748, Ruth L. Kirschstein National Research Service Award T32CA082088, and the Pin Down Bladder Cancer Fund.