〔Abstract〕 Objective To analyze the effect of heparin free dialysis filtration in patients with end-stage renal disease (ESRD) and upper gastrointestinal bleeding (UGB). Methods Thirty six patients with ESRD and UGB admitted to Sanming First Hospital Affiliated to Fujian Medical University from January 2019 to December 2022 were randomly selected and divided into a control group (routine heparin hemodialysis) and an observation group (heparin free dialysis filtration treatment) with 18 cases in each group. The hemostasis rate, clinical efficacy, 36–item short form health survey (SF-36) scores, and renal function indicators between two groups of patients were compared. Results There was no statistically significant difference in hemostasis rates between the two groups of patients on the first and second days (P > 0.05). The hemostatic rate of the observation group on the 3rd to 7th day was higher than that of the control group, and the difference was statistically significant (P < 0.05). The clinical treatment efficiency of the observation group patients was higher than that of the control group, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in the SF-36 scores between the two groups before treatment (P > 0.05); after treatment, the SF-36 score of the observation group was higher than that of the control group, and the difference was statistically significant (P < 0.05). Before treatment, there was no statistically significant difference in renal function indicators between the two groups (P > 0.05); after treatment, the renal function indicators of the observation group were lower than those of the control group, and the differences were statistically significant (P < 0.05). Conclusion Patients with ESRD and UGB treated with heparin free dialysis filtration have better hemostatic effects, significantly improving their quality of life, and effectively improving their renal function.