ABSTRACT: Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF.A longitudinal cohort.23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year.Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time.Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year.Among 23,645 included patients, 51% had substantial renal urea clearance (?3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (?3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d.Potential selection bias and wide CIs.Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.