Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963-2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010-2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9 > 10) was similar to National Health and Nutrition Examination Survey participants (7%, p = 0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p = 0.05). Postdonation predictors of depressive symptoms included nonwhite race OR = 2.00, p = 0.020), younger age at donation (OR = 1.33 per 10 years, p = 0.002), longer recovery time from donation (OR = 1.74, p = 0.0009), greater financial burden (OR = 1.32, p = 0.013) and feeling morally obligated to donate (OR = 1.23, p = 0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention. Using donor records, validated depression surveys, and donation experience questions from 2455 living kidney donors, the investigators find that most donors report emotional well-being years after donation, but for those with subsequent depression symptoms, identified predictors provide an opportunity for intervention.