BACKGROUND The association between cardiorespiratory fitness (fitness) and mortality is well described. However, the association between midlife fitness and the development of nonfatal chronic conditions in older age has not been studied. METHODS To examine the association between midlife fitness and chronic disease outcomes in later life, participant data from the Cooper Center Longitudinal Study were linked with Medicare claims. We studied 18 670 healthy participants (21.1% women; median age, 49 years) who survived to receive Medicare coverage from January 1, 1999, to December 31, 2009. Fitness estimated by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Eight common chronic conditions were defined using validated algorithms, and associations between midlife fitness and the number of conditions were assessed using a modified Cox proportional hazards model that stratified the at-risk population by the number of conditions while adjusting for age, body mass index, blood pressure, cholesterol and glucose levels, alcohol use, and smoking. RESULTS After 120 780 person-years of Medicare exposure with a median follow-up of 26 years, the highest quintile of fitness (quintile 5) was associated with a lower incidence of chronic conditions compared with the lowest quintile (quintile 1) in men (15.6 [95% CI, 15.0-16.2] vs 28.2 [27.4-29.0] per 100 person-years) and women (11.4 [10.5-12.3] vs 20.1 [18.7 vs 21.6] per 100 person-years). After multivariate adjustment, higher fitness (in METs) was associated with a lower risk of developing chronic conditions in men (hazard ratio, 0.95 [95% CI, 0.94-0.96] per MET) and women (0.94 [0.91-0.96] per MET). Among decedents (2406 [12.9%]), higher fitness was associated with lower risk of developing chronic conditions relative to survival (compression hazard ratio, 0.90 [95% CI, 0.88-0.92] per MET), suggesting morbidity compression. CONCLUSIONS In this cohort of healthy middle-aged adults, fitness was significantly associated with a lower risk of developing chronic disease outcomes during 26 years of follow-up. These findings suggest that higher midlife fitness may be associated with the compression of morbidity in older age.