Benefits of cardiorespiratory fitness on cardiovascular health are well recognized, but the impact on incidence of atrial fibrillation (AF) and stroke, and, particularly, risk of stroke and mortality in patients with AF is less clear. From 1993 to 2010, patients referred for a treadmill exercise test (TMET) at the Mayo Clinic Rochester, MN, were retrospectively identified (N = 76,857). From this, 14,094 local residents were selected. Exclusions were age less than 18 years; history of heart failure, structural or valvular heart disease, AF or flutter, or stroke. Subjects were divided into 4 groups at baseline based on quartiles of functional aerobic capacity (FAC) and followed through January 2016. The final study cohort included 12,043 patients. During median follow-up of 14 (9 to 17) years, 1,222 patients developed incident AF, 1,128 developed stroke, and 1,590 patients died. Each 10% increase in FAC was associated with decreased risk of incident AF, stroke, and mortality by 7% (0.93 [0.91 to 0.96, p less than 0.001]), 8% (0.92 [0.89 to 0.94, p less than 0.001]), and 16% (0.84 [0.82 to 0.86, p less than 0.001]), respectively. In patients who developed incident AF with baseline FAC less than 75% versus greater than or equal to 105%, risks of both stroke (1.40 [1.04 to 1.90, p = 0.01]) and mortality (3.20 [2.11 to 4.58, p less than 0.001]) were significantly higher. In conclusion, better cardiorespiratory fitness is associated with lower risk of incident AF, stroke, and mortality. Similarly, risk of stroke and mortality in patients with AF is also inversely associated with cardiorespiratory fitness.