Fatigue of striated muscles is defined as the impossibility to generate the expected or required force during the repeated contraction. During the maximal voluntary teeth contraction in the position of central occlusion the initial fatigue in masticatory muscles during the isometric contraction occurs. If a person can clench its teeth continuously and voluntarily it has a diagnostic significance since the peripheral fatigue is that important factor in the masticatory muscles activity, which is in direct correlation with the function of the masticatory system. The aim was to compare the obtained results of the initial fatigue of masseter muscles during the maximal voluntary teeth contraction in subjects with naturally healthy intact dentition and subjects with a pair of new full dentures. The investigation comprised 20 subjects with healthy stomatognathic system of the skeletal class I by Angle. Comparison of the values of the obtained results was performed electromyographically by synchronous registration of action potentials of masseter muscles. Results of the investigation of the onset of initial fatigue of masseter muscles in the subjects with natural healthy intact dentitions showed lower values, i.e., faster development of the muscular fatigue (31.5 s) compared to the subjects with a pair of new full dentures (44.5 s).