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Few studies have investigated long-term changes in cardiorespiratory fitness (CRF), defined by indirect measures of CRF, and all-cause mortality. We aimed to investigate whether long-term change in CRF, as assessed by the gold standard method of respiratory gas exchange during exercise, is associated with all-cause mortality. A population-based sample of 579 men aged 42 to 60 years with no missing data at baseline examination (V1) and at reexamination at 11 years (V2) were included. Maximal oxygen uptake (VO_2max) was measured at both visits using respiratory gas exchange during maximal exercise testing, and the difference (ΔVO_2max) was calculated as VO_2max (V2) − VO_2max (V1). Deaths were ascertained annually using national death certificates during 15 years of follow-up after V2. The mean ΔVO_2max was −5.2 mL/min*kg. During median follow-up of 13.3 years (interquartile range, 12.5-14.0 …