Unilateral onset and persistent asymmetry of motor signs are unique features of PD. The dominant hemisphere may have more efficient motor networks with greater neural reserve to cope with pathological changes. Therefore, this study compared dominant-side onset and non-dominant-side onset PD to evaluate whether dominant-side onset patients have greater neural reserve and fewer motor deficits despite similar pathological changes.We included the data of 157 consecutive, de novo PD patients with documented right-handedness who underwent dopamine transporter PET scans for an initial diagnostic workup. Among them, 118 patients with significant asymmetric motor deficits were selected for the analyses.Dominant-side patients (i.e., the majority of motor deficits on the right side) showed significantly fewer motor deficits (i.e., the part III score of the UPDRS) than non-dominant-side patients (18.0 ± 8.1 and 22.9 ± 10.1, respectively; P = 0.005). Other variables, including symptom duration and striatal dopaminergic activities, were similar between the two groups. A general linear model showed that this difference in motor deficits remained statistically significant after controlling for patient age, sex, symptom duration, and striatal dopaminergic activity in the posterior putamen (P = 0.013).These results suggest that dominant-side patients have greater neural reserve, allowing them to better cope with PD-related pathological changes (i.e., fewer motor deficits despite similar dopamine reduction) compared to non-dominant-side patients.