OBJECTIVE: Vascular complications of diabetes have declined substantially over the past 20 years. However, the impact of modern medical treatments on infectious diseases in people with diabetes remains unknown. RESEARCH DESIGN AND METHODS: We estimated rates of infections requiring hospitalizations in adults (≥18 years) with versus without diabetes, using the 2000-2015 National Inpatient Sample and the National Health Interview Surveys. Annual age-standardized and age-specific hospitalization rates in groups with and without diabetes were stratified by infection type. Trends were assessed using Joinpoint regression with the annual percentage change (Δ%/year) reported. RESULTS: In 2015, hospitalization rates remained almost four times as high in adults with versus without diabetes (rate ratio 3.8 [95% CI 3.8-3.8]) and as much as 15.7 times as high, depending on infection type. Overall, between 2000 and 2015, rates of hospitalizations increased from 63.1 to 68.7 per 1,000 persons in adults with diabetes and from 15.5 to 16.3 in adults without diabetes. However, from 2008, rates declined 7.9% in adults without diabetes (from 17.7 to 16.3 per 1,000 persons; Δ%/year -1.5, P < 0.01), while no significant decline was noted in adults with diabetes. The lack of decline in adults with diabetes in the later period was driven by significant increases in rates of foot infections and cellulitis as well as by lack of decline for pneumonia and postoperative wound infections in young adults with diabetes. CONCLUSIONS: Findings from this study highlight the need for greater infectious risk mitigation in adults with diabetes, especially young adults with diabetes.