Abstract Introduction The need for kidney donations in patients with end-stage kidney disease has continued to exceed the number of deceased donor transplants, signifying the need for the continued growth, sustainability, and success of living kidney donation. Following donation, living kidney donors have excellent survival rates with mixed data regarding long-term outcomes of renal failure, hypertension, and proteinuria. However, no studies to our knowledge have looked at differences in the development of long-term sexual dysfunction following living kidney donation, a potentially serious quality of life issue. Objective To analyze differences in five-year sexual dysfunction outcomes among male and female living kidney donors using the US Collaborative Network within the TriNetX database, a federated network of EMR data from multiple healthcare organizations across the United States. Methods We used the TriNetX database to perform a propensity score-matched cohort study comparing five-year outcomes of sexual dysfunction development among adult (≥18) male living kidney donors (Male) and female living kidney donors (Female) from December 2013 to December 2022. Living kidney donors were defined as the presence of one diagnostic code and one procedural code. Patients were excluded from the study if they had any instance of diagnosed transplant status (by ICD-10) or transplantation procedures (by CPT) prior to the kidney donor status. Patients were matched on age, sex, race, ethnicity, marital status, diabetes mellitus, cardiovascular disease, personal history of genitourinary disease, presence of urogenital implants, mood disorders, BMI, tobacco and alcohol use, and problems related to lifestyle and socioeconomic circumstances. Primary outcomes analysis included 5-year hazard ratio of diagnosed decreased libido, sexual dysfunction (composite of new diagnosed male ED, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders, or unspecified), UTI, and STDs. Secondary outcomes included sex counseling or problems in relationship with spouse or partner. Results There were 2,821 patients in each cohort after matching (Male, Female). Mean age of the cohort was 42.7 ± 12.7, 73.3% were White, and 10.8% were Hispanic/Latino (p >0.05). At 5-years, Kaplan-Meier analysis revealed that the Male donor cohort had a significantly higher hazard ratio (HR) than Female donors for sexual dysfunction (HR: 3.006, 95% Confidence Interval [CI]: 1.761,5.131). Between the cohorts, 39 (1%) Male patients developed ED and ~10 (<1%) Female patients developed vaginismus/dyspareunia within 5 years. No significant difference was found for the development of sexual arousal disorders/desire disorders (0.17% vs 0.06%, p = 0.052), orgasmic disorders (0.03% vs 0.03%, p = 0.99), decreased libido (0.48% vs 0.85%, p =0.94) and STD’s (0.72% vs 0.89%, p = 0.70). For secondary outcomes, no significant difference was found for the 5-year hazard of need for sex counseling or interpersonal relationship issues. Conclusions In our analysis of this large, real-world database, we found that male living kidney donors had higher rates of sexual dysfunction development 5-years post-living kidney donation. While living kidney donation is a safe, viable, and excellent alternative to deceased kidney donation, clinicians and living donors should both be aware about the potential association of developing sexual dysfunction post-donation. Disclosure No.