Several studies have identified higher mortality for patients admitted as emergencies at the weekend compared with emergency admissions during the week, but most have focused on specific conditions or have had a limited sample size. Using routinely collected hospital administrative data, we examined in-hospital deaths for all emergency inpatient admissions to all public acute hospitals in England for 2005/2006. Odds of death were calculated for admissions at the weekend compared to admissions during the week, adjusted for age, sex, socioeconomic deprivation, comorbidity and diagnosis. Of a total of 4,317,866 emergency admissions, we found 215,054 in-hospital deaths with an overall crude mortality rate of 5.0% (5.2% for all weekend admissions and 4.9% for all weekday admissions). The overall adjusted odds of death for all emergency admissions was 10% higher (OR 1.10, 95% CI 1.08 to 1.11) in those patients admitted at the weekend compared with patients admitted during a weekday (p<0.001). This is the largest study published on weekend mortality and highlights an area of concern in relation to the delivery of acute services.