© 2021 by Turkish Association of Neuropsychiatry.Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease that starts unilaterally in almost all cases and tends to emerge on the side of the dominant hand, but what we know about the cause of this lateralization is limited. Frequent use of the extremity and physical activity are argued to be protective from PD in preclinical and clinical studies. This study aimed to evaluate the effect of handedness and working in occupations that require continuous use of upper extremities on the disease onset-side. Methods: We retrospectively collected 84 PD patients who applied to Koç University Neurology outpatient clinic between July 2016-October 2018. We analyzed the parameters of the side and region of disease onset, age of onset, number of drugs used for PD, hand preference, and patients’ occupations. Results: The median age of our study group was 61 (53–69). Thirty (36%) of the 84 patients were women. Seventy-nine patients (94%) were right-handed. Eighty-three (99%) had asymmetric onset. The disease started on the dominant hand side in 47 patients (57%) and on the non- dominant hand side in 36 (43%) patients. In our group with a median disease duration of four (2–7) years, the side with more severe complaints measured with the Unified Parkinson’s Disease Evaluation Scale was consistent with the onset-side of the disease (p<0.001). In addition, the number of drugs used for PD and the scale score were higher in patients with longer disease duration (p=0.039, p=0.005). The number of drugs used for PD was also higher in patients with lower extremity-onset or both upper and lower extremities affected simultaneously than the upper extremity-onset (p=0.005). While the probability of starting on the dominant side was 43% in patients working in occupations requiring continuous use of upper extremities, it was 65% in others (p=0.027). Conclusion: According to this study, the onset of PD tends to be on the dominant hand side. Continuous upper extremity use may reduce the possibility of starting on the dominant side.