The main purpose of this study was to evaluate the relationship between different methods proposed by the American College of Sports Medicine (ACSM) to prescribe exercise intensity using heart rate (HR) and oxygen uptake (VO2) in obese individuals. Sixty-eight overweight to severely obese adults were divided into three groups (tertile) based on their BMI. The groups were T1 group (BMI = 30.5 ± 1.5, n = 23), T2 group (BMI = 34.3 ± 1.0, n = 23), and T3 group (BMI = 40.2 ± 3.7, n = 22). All subjects performed a graded exercise test using a ramp protocol on a treadmill. Individual linear regressions between %HR reserve (%HRR) and %VO2 reserve (%VO2R), %HRR and %VO2 peak (%VO2peak), %maximal HR (%HRmax) and %VO2R, and %HRmax and %VO2peak were calculated. When all the subjects were grouped together, the %HRR–%VO2R mean regression was partially related to the line of identity, while the %HRR–%VO2peak, %HRmax–%VO2R, and %HRmax–%VO2peak mean regressions were all significantly different than the line of identity (P < 0.001). The degree of obesity accounted for ∼15% of the variation for both %HRR–%VO2R and %HRR–%VO2peak mean regressions. The %HRmax–%VO2R and %HRmax–%VO2peak mean regressions were not affected by the degree of obesity but resting HR accounted for 28–37% of the variation. The relationship between the exercise intensity determined by the %HRR–%VO2R and the %HRR–%VO2peak mean regression seems to be influenced by the degree of obesity. The degree of obesity does not affect the relationship between exercise intensity generated by the %HRmax–%VO2R or %HRmax–%VO2peak equations but the resting HR does.