Background: Relationship between BP variability and kidney function in living kidney donors (LKD) is unknown. We aim to examine the association between BP variability and the risk of worsening kidney function post-donation. Methods: A cohort study using OPTN/SRTR includes adult LKD undergoing donation between 6/1972 and 9/2022. Average real variability (ARV) defined as an average of absolute difference in consecutive BP at 6, 12 and 24 months post-donation was used for assessing BP variability and categorized into quartiles (Q) for SBP and DBP (AVR-SBP and AVR-DBP). The risks of ≥35% decrease in post-donation eGFR from pre-donation eGFR among the quartiles of AVR-SBP and AVR-DBP were evaluated by Cox regression. Results: Of 136,984 LKD, mean±SD age was 42±12 years and 6% were female. Mean pre-donation SBP and DBP were 122±13 and 74±9 mmHg, respectively. Median (IQR) ARV-SBP and ARV-DBP were 7 (3, 12) and 5.5 (2, 9.5), respectively. Median pre-donation eGFR was 98.33 (82.94, 116.66; P trend 0.110). Median eGFR at 6-, 12-, and 24-months post-donation were 57.58 (48.43, 68.89), 58.93 (49.53, 70.61), and 61.02 (51.34, 72.78) mmHg, respectively. Compared to Q1 of the ARV-SBP, only Q3 and Q4 had a 4-6% higher risk for declined eGFR (HR Q3 (95%CI) 1.04 (1.00, 1.08) and HR Q4 1.06 (1.02, 1.11)). After adjusting for age, gender, race/ethnicity, U.S. citizenship status, level of education, history of hypertension, pre-donation BMI, SBP, DBP, creatinine, proteinuria and the interaction term between ARV and age (<65 vs. ≥65), only Q4 remained to have significantly greater risk of the event (HR Q4 1.09 (1.03, 1.16)) and older LKD ≥65 years old had lower the risk compared to the younger (HR Q4-Age 0.75 (0.57, 0.98), P interaction 0.037). For ARV-DBP, Q2 and Q3 had 4-5% higher risk of the event compared to the Q1 (HR Q 2 1.04 (1.00, 1.08) and HR HR Q 3 1.05 (1.01, 1.09)) and only Q3 remained significantly having higher the risk after adjusting for confounders (HR Q 3 1.06 (1.00, 1.13); P interaction non-significance). Conclusions: ARV-SBP especially in <65 years old and ARV-DBP are associated with a higher risk for a decline in post-donation kidney function. Pathophysiological alteration with hyperfiltration after unilateral nephrectomy may involve BP variability related to kidney function.