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This study observed the effects of the Clark comfortable nursing approach on self-care ability, self-burden, treatment adherence, quality of life, and complications in hemodialysis patients with end stage renal failure (ESRF). Eighty-two patients with ESRF receiving hemodialysis treatment were included and allocated into control and intervention groups. The control group received conventional nursing care, while the intervention group received the Clark comfortable nursing approach. The self-care ability, self-burden, treatment adherence, quality of life scores before and after the nursing intervention, and the occurrence of complications in both groups were compared. After the intervention, the intervention group showed higher scores in each dimension and the total score of the Exercise of Self-Care Agency Scale compared to the control group. Both groups exhibited improvements in various scores and total scores; however, the intervention group had lower scores overall than the control group. Additionally, the intervention group had higher scores in diet, water intake, medication, and dialysis regimen. Additionally, both groups had significantly higher scores in all dimensions of the quality-of-life scale post-intervention, with the intervention group demonstrating markedly higher scores in all dimensions. The total incidence of complications in the intervention group was 9.76%, which was lower than the 29.27% observed in the control group. The Clark comfortable nursing approach applied to hemodialysis patients with ESRF can enhance self-care ability, improve quality of life, increase treatment adherence, and reduce the incidence of hemodialysis-related complications. This model is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]