Increasing hemodialysis frequency from three to six times per week improves left-ventricular mass and health-related quality of life; however, effects on survival remain uncertain. To study this, we identified 556 patients in the International Quotidian Dialysis Registry who received daily hemodialysis (more than five times per week) between 2001 and 2010. Using propensity score-based matching, we matched 318 of these patients to 575 contemporaneous patients receiving conventional (three times weekly) hemodialysis in the Dialysis Outcomes and Practice Patterns Study. All patients had session times of <5 h, and received dialysis in the clinic or hospital setting. Mortality rates between groups were compared using Cox proportional hazards regression. Mean dialysis frequency in the daily group was 5.8 sessions per week. Mean weekly treatment time was 15.7 h for daily and 11.9 h for conventional patients. During 1382 patient-years of follow-up, 170 patients died. Those receiving daily hemodialysis had a significantly higher mortality rate than those receiving conventional hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard ratio 1.6). Similar results were found in prespecified subgroup and sensitivity analyses. Unlike previous studies, we found that in-center daily hemodialysis was not associated with any mortality benefit. Thus, decisions to undertake daily hemodialysis should be based on quality-of-life improvements, rather than on claims of improved survival.