Hemodialysis patients have high rates of mortality that may be related to aspects of the dialytic procedure. In prior studies, shorter length dialysis sessions have been associated with decreased survival, but these studies may have been confounded by body size differences. Here we tested whether in-center three-times-weekly hemodialysis patients with adequate urea clearances but shorter dialysis session length is associated with mortality independent of body size. Data were taken from a large national cohort of patients from a large dialysis organization undergoing three-times-weekly in-center hemodialysis. In the primary analysis, patients with prescribed dialysis sessions greater and less than 240 min were pair-matched on post-dialysis weight as well as on age, gender, and vascular access type. Compared to prescribed longer dialysis sessions, session lengths less than 240 min were significantly associated with increased all-cause mortality (adjusted hazard ratio 1.26). The association was consistent across strata of age, gender, and dialysis post-weight. Secondary analyses found a dose-response between prescribed session length and survival. Thus, among patients with adequate urea clearance, shorter dialysis session lengths are associated with increased mortality independent of body weight.