OBJECTIVE - To test the association of fitness changes over 7 and 20 years on the development of diabetes in middle age. RESEARCH DESIGN AND METHODS - Fitness was determined based on the duration of a maximal graded exercise treadmill test (Balke protocol) at up to three examinations over 20 years from 3,989 black and white men and women from the Coronary Artery Risk Development in Young Adults study. Relative fitness change (percent) was calculated as the difference between baseline and follow-up treadmill duration/baseline treadmill duration. Diabetes was identified as fasting glucose ≥126 mg/dl, postload glucose ≥200 mg/dl, or use of diabetes medications. RESULTS - Diabetes developed at a rate of 4 per 1,000 person-years in women (n = 149) and men (n = 122), and lower baseline fitness was associated with a higher incidence of diabetes in all race-sex groups (hazard ratios [HRs] from 1.8 to 2.3). On average, fitness declined 7.6% in women and 9.2% in men over 7 years. The likelihood of developing diabetes increased per SD decrease (19%) from the 7-year population mean change (-8.3%) in women (HR 1.22 [95% CI 1.09 -1.39]) and men (1.45 [1.20 -1.75]) after adjustment for age, race, smoking, family history of diabetes, baseline fitness, BMI, and fasting glucose. Participants who developed diabetes over 20 years experienced significantly larger declines in relative fitness over 20 years versus those who did not. CONCLUSIONS - Low fitness is significantly associated with diabetes incidence and explained in large part by the relationship between fitness and BMI. © 2009 by the American Diabetes Association.