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A low level of cardiorespiratory fitness (CRF) is a strong and independent predictor of all-cause mortality in men; however, it is unknown whether a gradient of mortality risk exists within the lowest CRF category.A total of 6251 apparently healthy men (mean age, 48.7 ± 6.3 yr) completed a comprehensive baseline clinical examination, including a maximal treadmill exercise test at Cooper Clinic between 1971 and 2006. In accord with previous studies using this cohort, low CRF was defined as a treadmill time in the first quintile within each age category of 40–49, 50–59, and 60–69 yr. The low CRF cohort was then grouped by tertiles (low/low, LL; mid/low, ML; and high/low, HL) using the same age categories.After a mean follow-up period of 19.1 ± 10.4 yr, 1259 deaths occurred. Adjusted all-cause mortality rates were 57.0, 31.1, and 34.4 deaths per 10,000 man-years across LL, ML, and HL CRF categories for the 40- to 49-yr-old age group (P trend = 0.007). Similar trends were seen across low CRF categories for the 50- to 59-yr-old and 60- to 69-yr-old age groups (P trend = 0.02 and 0.09, respectively). When using treadmill time as a continuous variable, each 1-min increment in treadmill time was associated with a 9%, 11%, and 15% reduction in risk of all-cause mortality among low-CRF men in the 40–49, 50–59, and 60–69 age groups, respectively.An inverse trend in all-cause mortality exists among men across LL, ML, and HL CRF groups. Although all low-fit men should be targeted for physical activity intervention, it is especially important to target the LL CRF group.