OBJECTIVES: This study examined the mortality and prevalence of Major Depressive Disorder (MDD) in the US Medicare population. METHODS: A retrospective study was performed in the US Medicare fee-for-service (FFS) population from 2008-2013. MDD patients were identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes 296.2x and 296.3x. Patients with continuous Medicare FFS enrollment from 2008-2013 were included. Any managed care enrollment during this period was not permitted. MDD prevalence was stratified by age, gender, race and state, and the age- and sex-adjusted prevalence (overall and specified by age group and sex) were calculated by direct standardization to the US population aged 65 years or older in 2010 using sex-specific age groups. RESULTS: The 30-day mortality rates were stable from 2008-2013 (3 per 1000 persons). However, 1-year mortality rates decreased by 11.8% (17 to 15 per 1000 persons) from 2008 through 2013. Overall prevalence was 3.28% in 2008, 3.73% in 2009, 4.12% in 2010, 4.46% in 2011, 4.72% in 2012, and 4.96% in 2013. Prevalence rates were higher among women than men throughout the study period. MDD patients aged 90 years or older had the highest prevalence rates during the study period, ranging from 4.43% in 2008, to 7.22% in 2013. Prevalence rates rose steadily among all age groups from 2008 to 2013. Hispanic patients had the highest prevalence throughout the study period, ranging from 5.6% in 2008 to 7.3% in 2013. Patients residing in Massachusetts had the highest prevalence rates throughout the study period, ranging from 4.9%-7.4%.  CONCLUSIONS: Adjusted mortality rates were stable, with a steady increase in the prevalence of MDD from 2008 through 2013. In addition, Hispanic female patients aged 90 years or older who resided in Massachusetts were more likely to have MDD.