Objectives: Our objective was to explore factors influencing health-related quality of life in livingdonor kidney transplant recipients. Materials and Methods: A total of 140 kidney transplant recipients, enrolled between December 2014 and April 2015, were administered questionnaires on medical outcomes, 36-item Short Form Health Survey, medical coping modes, cognitive appraisal of health scale, and adverse effects of medications. Path analysis was employed to verify the hypothesized model. Results: Increased serum creatinine level and high economic burden had direct positive effects on negative appraisal (β = 0.18, P < .05 and β = 0.46, P < .01). Adverse effects of medication had direct positive effects on confrontation; whereas negative appraisal had direct positive effect on acceptance-resignation (β = 0.21, P < .05) and direct negative effect on physical component summary (β = -0.43, P < .001) and mental component summary (β = -0.51, P < .001). In addition, confrontation directly affected mental component summary (β = -0.15, P < .05). The enrolled variables accounted for 25.0% of physical component summary variance and 35.4% of mental component summary variance. Conclusions: In this study, economic burden, serum creatinine levels, and adverse effects of immunosuppressive therapy were the key external factors, whereas patients' cognitive appraisal and coping strategies were the main internal factors affecting patients' health-related quality of life. Medical care providers attending to transplant recipients should be able to identify patients developing negative coping strategies in response to stressors and plan individualized counseling programs for these patients.