Data on the effect of trajectories in long-term glycemia and all-cause mortality are lacking. The authors studied the effect of trajectories in long-term glycemic control on all-cause mortality in patients with type 2 diabetes. A cohort of 8,812 veterans with type 2 diabetes was assembled retrospectively using Veterans Affairs registry data. For each veteran in the cohort, a 3-month person-period data set was created from April 1997 to May 2006. The average duration of follow-up was 4.5 years. The overall mortality rate was 15.3%. Using a novel approach for joint modeling of time to death and longitudinal measurements of hemoglobin A1c (HbA1c) level, after adjustment for all significant baseline covariates, baseline HbA1c was found to be significantly associated with mortality (hazard ratio = 2.1, 95% confidence interval: 1.3, 3.6) (i.e., a 1% increase in baseline HbA1c level was associated with an average 2-fold increase in mortality risk). Similarly, the slope of the HbA1c trajectory was marginally significantly associated with mortality (hazard ratio = 7.3, 95% confidence interval: 0.9, 57.1) after adjustment for baseline covariates (i.e., a 1% increase in HbA1c level over 3 months was associated with a 22% increase in mortality risk). The authors conclude that a positive trajectory of long-term hyperglycemia is associated with increased mortality.