Daily preferential use was shown to alter physiological and mechanical properties of skeletal muscle. This study was aimed at revealing differences in the control strategy of muscle pairs in humans who show a clear preference for one hand. We compared the motor unit (MU) recruitment and firing behavior in the first dorsal interosseous (FDI) muscle of both hands in eight male volunteers whose hand preference was evaluated with the use of a standard questionnaire. Myoelectric signals were recorded while subjects isometrically abducted the index finger at 30% of the maximal voluntary contraction (MVC) force. A myoelectric signal decomposition technique was used to accurately identify MU firing times from the myoelectric signal. In MUs of the dominant hand, mean values for recruitment threshold, initial firing rate, average firing rate at target force, and discharge variability were lower when compared with the nondominant hand. Analysis of the cross-correlation between mean firing rate and muscle force revealed cross-correlation peaks of longer latency in the dominant hand than in the nondominant side. This lag of the force output with respect to fluctuations in the firing behavior of MUs is indicative of a greater mechanical delay in the dominant FDI muscle. MVC force was not significantly different across muscle pairs, but the variability of force at the submaximal target level was higher in the nondominant side. The presence of lower average firing rates, lower recruitment thresholds, and greater firing rate/force delay in the dominant hand is consistent with the notion of an increased percentage of slow twitch fibers in the preferentially used muscle, allowing twitch fusion and force buildup to occur at lower firing rates. It is suggested that a lifetime of preferred use may cause adaptations in the fiber composition of the dominant muscle such that the mechanical effectiveness of its MUs increased.