This study examined the effect of aerobic interval training on cardiac adaptations in VLCAD-deficient mice and determined the effects of the deficiency on the morphology and function of the left ventricle among 53 knockout homozygous VLCAD-/-, 28 heterozygous VLCAD±, and 39 controls VLCAD+/+ male mice (129 SvJ/C57BL6). Echocardiographic images were used to determine the left ventricular (LV) wall thicknesses, during systole and diastole, acquired at a depth setting of 20 mm. Cardiac hypertrophy (as evidenced by increased wall thickness, and decreased left ventricular dimension in diastole and systole) appeared to be a major finding in the VLCAD-/- mouse with, however, normal %FS. The trained mice from all three genotypes exhibited lower body weight compared with their controls. The echocardiographic data of this study demonstrated structural but not functional differences among the three genotypes. This study demonstrated that VLCAD± deficient mice handled interval training similarly to the non-deficient mice. Four VLCAD-/- deficient mice died unexpectedly on the treadmill during the early stages of training. The VLCAD-/- deficient mice that survived adapted to the aerobic interval training similarly to the non-deficient mice. It is unclear whether aerobic interval training is an appropriate training tool for the VLCAD-deficient humans.