e24097 Background: Women with gynecological cancer (GynCa) reported an increased risk for acute and long-term sexual dysfunction across cancer treatments, especially radiation therapy (RT). However, limited data exist on the course of sexual dysfunction across RT and its risk factors are unknown. This study sought to characterize women’s sexual dysfunction trajectories and identified risk factors of persistent sexual dysfunction. Methods: Using a longitudinal study design, patient-reported sexual dysfunction, demographic and clinical data were collected. Women receiving RT for GynCa older than 18 years or age, race, and BMI matched healthy controls were enrolled. Female Sexual Function Index (FSFI) was used to assess women’s sexual dysfunction. Patients completed all the questionnaires pre-RT, at the end of RT, 6- and 12-month post-RT. Group-based trajectory modeling was used to identify trajectories of sexual dysfunction and risk factors of persistent sexual dysfunction. Results: Eighty-two patients were analyzed, including 36 GynCa patients receiving RT and 46 healthy post-menopausal women, comprising of 33 Blacks, 44 Whites, and 5 others. Three trajectory groups of sexual dysfunction (total FSFI score) were identified: low risk (17.4%), moderate risk (12.3%), and high risk (70.4%). All three trajectory groups were significantly different from each other (p<0.01). Similarly, three trajectories were identified for each of six FSFI domains: desire (low [6.3%], moderate [62.5%], high [31.2%], p<0.01); arousal (low [38.1%], moderate [46.4%], high [15.4%], p<0.01); lubrication (low [49.7%], moderate [44.6%], high [5.7%], p<0.01); orgasm (low [43.8%], moderate [31.3%], high [24.9%], p<0.01); pain (low [25.5%], moderate [64.2%], high [10.3%], p<0.01); and satisfaction (low [8.3%], moderate [61.4%], high [30.3%], p<0.01). Risk factors of sexual dysfunction were high pH (p=0.007) and without chemotherapy (p=0.019). Young women had more arousal (p=0.011); high education level was associated with high arousal (p=0.039); low pH was associated with high arousal (p=0.018) and orgasm (p=0.036). No risk factors were found for desire and satisfaction domains. BMI, surgery, and study cohort (cancer vs healthy) were not predictors of sexual dysfunction trajectories. Conclusions: This study identified three trajectories of sexual dysfunction. Low education, high pH, no chemotherapy, and elder women were risk factors of severe sexual dysfunction. Sexual dysfunction interventions should address these risk factors.