ABSTRACT Background Recent examination of the STEADY‐PD III isradipine clinical trial data concluded that early‐stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of the trial. These findings suggest that greater exposure to isradipine might slow disease progression. Objectives To test this hypothesis, the data from the STEADY‐PD II isradipine clinical trial, in which an extended‐release (ER) formulation of the drug was used, was re‐examined. Methods The re‐analysis of the STEADY‐PD II data was restricted to participants assigned placebo or tolerable isradipine treatment (10 mg isradipine/day or less). The effect of isradipine treatment was assessed by Unified Parkinson's Disease Rating Scale (UPDRS) at the end of the 52‐week trial, rather than by last observation carried forward at the beginning of symptomatic therapy. Results Participant cohorts were well‐matched for baseline disability, initial disease progression, and time to initiation of symptomatic therapy. Participants given 10 mg/day ER isradipine had significantly smaller total and part 3 UPDRS scores at the end of the trial than did the placebo cohort. Post hoc adjustment for symptomatic therapy diminished the statistical significance of these differences. In those participants not taking a monoamine oxidase B inhibitor, the progression in UPDRS scores also was significantly reduced. Conclusions These results are consistent with the recent secondary analysis of the STEADY‐PD III clinical trial—suggesting that clinically attainable brain exposure to isradipine may slow early‐stage PD progression. © 2021 International Parkinson and Movement Disorder Society