Levodopa is the first-line treatment for patients with Parkinson's disease (PD). However, only a few studies have focused on the tolerance of this drug in older patients with PD in the early and middle stages. Therefore, this study aimed to explore the effects of different levodopa doses on blood pressure (BP) in this subpopulation.This cohort analysis enrolled 83 patients. The levodopa challenge test was used to evaluate drug responsiveness. After at least 12 h following anti-PD drug discontinuation, patients' BPs were measured in a lying position, after 1 min standing, and after 3 min standing, in "off state" and best "on state."BP in the 250 mg and 375 mg levodopa/benserazide groups decreased significantly in the lying and standing positions. The 3-min standing-position systolic BP was significantly influenced by the dose of levodopa/benserazide. However, no statistical change was observed in the 125 mg group. The postural-mediated systolic BP disparity was significant at 3 min in the upright position. Nineteen (incidence, 22.9%) and Twenty-five patients (incidence, 30.1%) developed complications of orthostatic hypotension (OH) in the "off state" and best "on state," respectively. Mild cognitive impairment was a risk factor for OH occurrence in the "off state." The OH occurrence in the best "on state" was associated with OH in the "off state" and urinary incontinence.Our findings suggest that 250 mg or more of levodopa/benserazide could significantly reduce BP and orthostatic effect in older patients with PD in the early and middle stages. Therefore, they should routinely monitor their BP.ChiCTR2200055707.© 2023 The Authors.