A poor Fitness Fatness Index (FFI) is associated with type 2 diabetes incidence, other chronic conditions (Alzheimer’s, cancer, and cardiovascular disease) and all-cause mortality. Recent investigations have proposed that an individualised exercise prescription based on ventilatory thresholds is more effective than a standardised prescription in improving cardiorespiratory fitness (CRF), a key mediator of FFI. Thus, the aim of the current study was to determine the effectiveness of individualised versus standardised exercise prescription on FFI in sedentary adults. Thirty-eight sedentary individuals were randomised to 12-weeks of: (1) individualised exercise training using ventilatory thresholds (n = 19) or (2) standardised exercise training using a percentage of heart rate reserve (n = 19). A convenience sample was also recruited as a control group (n=8). Participants completed CRF exercise training three days per week, for 12-weeks on a motorised treadmill. FFI was calculated as CRF in metabolic equivalents (METs), divided by fatness determined by waist to height ratio (WtHR). A graded exercise test was used to measure CRF, and anthropometric measures (height and waist circumference) were assessed to ascertain WtHR. There was a difference in FFI change between study groups, whilst controlling for baseline FFI, F (2, 42) = 19.382 p < .001, partial η2 = 0.480. The magnitude of FFI increase from baseline was significantly higher in the individualised (+15%) compared to the standardised (+10%) (p = 0.028) and control group (+4%) (p = <.001). The main finding of the present study is that individualised exercise prescription had the greatest effect on improving FFI in sedentary adults compared to a standardised prescription. Therefore, an individualised based exercise prescription should be considered a viable and practical method of improving FFI in sedentary adults.