The management of patients admitted during weekends may be compromised because the level of staffing in the hospital is often lower then. This study was conducted to assess what independent influence, if any, weekend admission might have on inhospital mortality. The authors analyzed the clinical data of 429,880 adults >14 years of age who were admitted to internal medicine wards in Spain after having presented to the hospitals' emergency departments. Overall mortality and early mortality (occurring in the first 48 hours) were examined, taking into account whether a patient was admitted on a weekend or a weekday, in addition to other parameters. Weekend admissions were associated with a significantly higher inhospital mortality than weekday admissions among patients admitted to an internal medicine service (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.14-1.08). Differences in mortality persisted after adjustment for age, sex, and coexisting disorders (OR = 1.071; 95% CI = 1.046-1.097). Analyses of deaths within 2 days after admission showed larger relative differences in mortality between weekend and weekday admissions (OR = 1.28; 95% CI = 1.22-1.33). For patients admitted to an internal medicine service via an acute care visit to the emergency room, admission on weekends is associated with higher mortality than admission during the week.