Key Points: Health-related quality of life in dialysis depends on many nonclinical factors. Psychosocial determinants contribute to explaining variance in health-related quality-of-life domains better than demographic and medical variables alone. In comparison with past small-scale studies, self-efficacy showed significant associations with all aspects of health-related quality of life. Background: We investigated whether psychosocial determinants self-efficacy and social support are associated with health-related quality of life in patients on hemodialysis enrolled in the CONVINCE trial. Methods: We used baseline data from the cohort of patients involved in the CONVINCE randomized trial of hemodiafiltration versus hemodialysis. Measures included age, sex, relationship status, children, housing, education, employment, comorbidities, dialysis schedules, time of first dialysis, residual kidney function, general self-efficacy and social support scores, and Patient-Reported Outcomes Measurement Information System measurements for health-related quality of life. Associations were analyzed using hierarchical regression. Results: One thousand three hundred sixty patients from the CONVINCE trial were the cohort of interest. The mean age was 62±13.5 years (range, 20–92), and 66.9% were male. Self-efficacy was a significant predictor for all health-related quality-of-life domains: depression (β=−0.36, P < 0.001), anxiety (β=−0.35, P < 0.001), social participation (β=0.32, P < 0.001), cognition (β=0.29, P < 0.001), fatigue (β=−0.29, P < 0.001), physical function (β=0.27, P < 0.001), sleep disturbance (β=−0.23, P < 0.001), pain interference (β=0.21, P < 0.001), pain intensity (β=−0.17, P < 0.001), interdialytic symptoms (β=−0.14, P = 0.002), and intradialytic symptoms (β=−0.14, P = 0.002). Social support was a significant predictor for cognition (β=0.21, P < 0.001), sleep disturbance (β=−0.11, P = 0.017), and intradialytic symptoms (β=−0.11, P = 0.02). Conclusions: Higher general self-efficacy scale scores are associated with improvements in cognition, depression, anxiety, social participation, fatigue, physical function, sleep disturbance, pain interference, interdialytic symptoms, pain intensity, and intradialytic symptoms. Associations for self-efficacy are larger than those for social support and stronger than previously reported. It is plausible that targeted psychosocial interventions may improve health outcomes in people on hemodialysis. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2025_01_30_KID0000000599.mp3

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