Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan’s National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients’ clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26–0.67, p < 0.001; aHR = 0.61, 95% CI 0.43–0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54–0.89, p = 0.005respectively]. In the patients who had a CHA₂DS₂-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36–0.83, p = 0.005; aHR = 0.72, 95% CI 0.52–1.00, p = 0.048; and aHR =0.73, 95% CI 0.58–0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.