Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This study aims to evaluate the direct medical costs of patients with PD using a large sample from an entire city and to identity the potential factors correlating with their inpatient costs in Guangzhou City, Southern China. Methods: This retrospective cross-sectional study uses data obtained from the Urban Employee-based Basic Medical Insurance (UEBMI) and the Urban Resident-based Basic Medical Insurance (URBMI) administrative claims databases in Guangzhou City from 2008 to 2012. The total sample was comprised of 2660 patients with PD. Costs were evaluated for the total sample and by types of insurance. The composition of costs was compared between the UEBMI and URBMI subgroups. The extended estimating-equations model was applied to identify the potential impact factors influencing the inpatient costs. Results: The direct medical costs per patient with PD were CNY 14,514.9 (USD 2299.4) in 2012, consisting of inpatient costs of CNY 13,551.4 and outpatient costs of CNY 963.5. The medication costs accounted for the largest part (50.3%). The inpatient costs of PD patients under the UEBMI scheme (CNY 13,651.0) were significantly higher than those of patients in the URBMI subgroup (CNY 12,402.2) (p < 0.05). The proportion of out-of-pocket spending out of inpatient and outpatient costs for UEBMI beneficiaries (24.3% and 56.1%) was much lower than that for patients under the URBMI scheme (47.9% and 76.2%). The regression analysis suggested that types of insurance, age, hospital levels, length of stay (LOS) and comorbidities were significantly correlated with the inpatient costs of patients with PD. Conclusions: The direct medical costs of patients with PD in China were high compared to the GDP per capita in Guangzhou City and different between the two evaluated types of insurance. Patients with the UEBMI scheme, of older age, with comorbidities, staying in tertiary hospitals and with longer LOS had significantly higher inpatient costs. Thus, policymakers need to reduce the gaps between the two urban insurance schemes in benefit levels, provide support for the development of a comprehensive long-term care insurance system and promote the use of telemedicine in China.