Background: Coronary microvascular dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in individuals with coronary artery disease (CAD). This study assessed CMD using combined dipyridamole‐exercise stress echocardiography (DExE) and myocardial strain/work to evaluate the impact on left ventricular (LV) function. Methods: This prospective study enrolled CAD individuals who underwent left anterior descending artery PCI and DExE assessment at 3 months post‐PCI to evaluate myocardial strain/work parameters at rest and stress. The primary endpoint was adverse clinical events, and the secondary endpoint was Seattle Angina Questionnaire (SAQ) health status at 1‐year. Results: The cohort comprised 84 individuals (54 ± 10 years, 17.9% female). Participants were stratified into two groups by coronary flow velocity reserve (CFVR): CFVR ≥ 2.5 group ( n = 63) and CFVR < 2.5 group ( n = 21). Compared with the CFVR ≥ 2.5 group, the CFVR < 2.5 group showed impaired LV functional reserve, with lower global longitudinal strain (GLS), global work index (GWI), and global work efficiency (GWE) at peak exercise and recovery, lower peak exercise global constructive work (GCW), higher recovery global wasted work (GWW), and smaller absolute changes ΔE—R (difference before vs. after exercise stress) in GLS, GWI, and GCW (all p < 0.05). In multivariable analysis, peak exercise GCW, recovery GWW, and ΔGCW (E − R) were independent predictors of CMD. At 1 year, no adverse clinical events occurred, and the CFVR ≥ 2.5 group had higher SAQ physical limitation (92.86 ± 11.38 vs. 82.14 ± 17.93), quality of life (95.63 ± 10.57 vs. 83.33 ± 19.90), and summary score (94.05 ± 8.51 vs. 85.71 ± 15.71) than the CFVR < 2.5 group (all p < 0.05). Conclusions: Combined DExE with myocardial strain/work analysis effectively evaluates LV function in CMD. Decreased CFVR post‐PCI is associated with impaired LV function and worse 1‐year quality of life outcomes, underscoring the need for close cardiac function monitoring in post‐PCI CMD individuals. Trial Registration: URL: https://www.chictr.org.cn/ ; Unique identifier: ChiCTR2500103229.

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