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The aims of this study were to investigate the long-term effects of living donor liver transplantation (LDLT) on the health-related quality of life (HRQOL) of donors with the Short Form 36 health survey and to determine the risk factors for poor outcomes. Between June 1990 and June 2004, LDLT was performed 1000 times at Kyoto University Hospital. In July 2005, 997 of the 1000 donors were contacted by mail so that data on their HRQOL could be collected. In all, 578 donors responded (ie, there was a 58.0% response rate). The norm-based HRQOL scores for donors were better than the scores for Japanese norms across all time periods. All scores were similar for left lobe donors (n = 367) and right lobe donors (n = 211). For all donors, a multivariate logistic regression analysis revealed that age, the number of months until recovery to the preoperative health status, hospital visits due to donation-related symptoms, rest from work related to donation in the past month, and the existence of 2 or more comorbidities were significantly associated with decreased HRQOL scores. Postoperative complications and recipient mortality were not predictors of poor HRQOL. In conclusion, HRQOL was better for both right lobe donors and left lobe donors versus the Japanese norm population in the long term (mean postdonation period = 6.8 years). However, the prolongation of symptoms or sequelae related to donation lowered mental health or social functioning. The emergence of comorbidities after donation also significantly affected HRQOL in the long term. Careful follow-up and sustained counseling are required for donors with risk factors for lower HRQOL. Liver Transpl 18:1343–1352, 2012. © 2012 AASLD.