Excess mortality and hospitalization have been identified after the 2-day gap in thrice-weekly hemodialysis patients compared with 1-day intervals, although findings vary internationally. Here we aimed to identify factors associated with mortality and hospitalization events in England using an incident cohort of 5864 hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry linked to hospitalization data. Higher admission rates were seen after the 2-day gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday or Tuesday (2.4 per year after the 2-day gap vs. 1.4 for the rest of the week, rate ratio 1.7). The greatest differences in admission rates were seen in patients admitted with fluid overload or with conditions associated with a high risk of fluid overload. Increased mortality following the 2-day gap was similarly independent of session pattern (20.5 vs. 16.7 per 100 patient years, rate ratio 1.22), with these increases being driven by out-of-hospital death (rate ratio 1.59 vs. 1.06 for in-hospital death). Non-white patients had an overall survival advantage, with the increased mortality after the 2-day gap being found only in whites. Thus, fluid overload may increase the risk of hospital admission after the 2-day gap and that the increased out-of-hospital mortality may relate to a higher incidence of sudden death. Future work should focus on exploring interventions in these subgroups.