Modality comparisons focusing on survival outcomes of nocturnal hemodialysis (NHD) or short daily hemodialysis (SDHD) versus other treatment paradigms of end-stage renal disease (ESRD) are sparse. The existing literature consists of cohort studies that are small, retrospective, underpowered, and poorly controlled. The only randomized controlled trial that included mortality as part of a complex composite endpoint is unable to provide information on survival only. Even if concerns with internal validity of this literature are set aside, the generalizability of a few hundred NHD and SDHD patients is an important consideration as it remains uncertain whether or not the purported survival benefits of intensive hemodialysis readily translate into similar benefits for the global ESRD population. The most feasible and definitive study design to compare NHD or SDHD to other treatment modalities (and to each other) is a large, prospective, matched cohort study.