Purpose <p>Chronic kidney disease (CKD) is a global health issue, and hemodialysis (HD) is the most commonly used dialysis method. Incremental HD has been proposed as an alternative, but evidence on its safety and benefits is limited. This study compared residual kidney function (RKF) preservation in patients undergoing incremental versus standard HD, also evaluating quality of life, hospitalizations and mortality.</p> Methods <p>This retrospective, longitudinal, observational case-control study included stage 5 CKD patients who started either incremental or standard HD between January 2021 and January 2023. The case group included patients who began incremental HD (2 weekly sessions lasting 4&#xa0;h or 3 weekly sessions lasting &lt; 3.5&#xa0;h), and the control group included patients who started standard HD schedule (thrice-weekly, minimum 4-hour sessions). The groups were matched by age, sex, underlying disease, comorbidities, and baseline lab values.</p> Results <p>80 patients were included (50% male; mean age 63.8 ± 11.9 years). Diabetes (32.5%) and hypertension (22.5%) were the main underlying conditions. Over two years, 3.8% had kidney transplants, 6.2% died, and 2.5% recovered kidney function. 45% of incremental HD patients retained RKF; none did in the standard HD schedule group. Incremental group had fewer infections, longer time free from loss of RKF than control group and better quality of life. No differences were found in cardiovascular events, mortality, or transplantation. RKF preservation was associated with incremental HD, higher albumin, and absence of bloodstream infections.</p> Conclusion <p>Starting HD with an incremental may better preserve RKF without compromising survival, while improving quality of life. Further clinical trials are needed to evaluate the safety and effectiveness of incremental HD and support its broader, patient-centered use.</p> Clinical trial number <p>Not applicable.</p>