Context: Glucose variability (GV) is common among hospitalized patients, but the prognostic implications are not understood. Objective: Investigate the association between GV, hospital length of stay (LOS), and mortality. Methods: GV was assessed by coefficient of variance (CV) and standard deviation (SD) of glucose values during hospitalization. Setting: Historical prospectively collected data of patients hospitalized between January 2011 and December 2013. Patients: Patients 18 years old. Main outcome: LOS, and in-hospital and mortality at end of follow-up. Results: The cohort included 20,303 patients (mean age 6 SD, 70 6 17 years; 51% men; median follow-up, 1022 days), of whom 8565 patients (42%) had diabetes mellitus (DM). Mean LOS was longer with higher CV or SD tertiles in patients without and with DM. In-hospital mortality was 8.2%, associated with higher tertiles of CV (4%, 10%, 19%) and SD (4%, 11%, 21%) in patients without DM and with DM (3%, 5%, 10%; and 2%, 4%, 9%, respectively). Mortality at the end of follow-up was increased in patients without DM with higher CV (28%, 42%, 55%) and SD (28%, 44%, 57%) tertiles and in patients with DM (26%, 35%, 45%; and 25%, 34%, 44%, respectively). Multivariate analysis indicated increased risk for in-hospital and end of follow-up mortality, in both groups. Adjustment for glucocorticoid treatment or hypoglycemia did not affect the results. Glucose levels during hospitalization and GV were two independent factors affecting LOS and in-hospital mortality. In each CV tertile, mortality was higher with median glucose 180 mg/dL, compared with ,180 mg/dL. Conclusions: In hospitalized patients with and without DM, increased GV is associated with longer hospitalization and increased short-and long-term mortality.