PurposeThe effect of aspirin therapy in patients with nonobstructive coronary artery disease (CAD) remains controversial. This study aimed to investigate the association between aspirin therapy and prognosis in nonobstructive CAD.MethodsWe searched for observational cohort studies on Pubmed, Embase, the Cochrane Library and Web of Science. Studies were included that compared the endpoint differences in patients with nonobstructive CAD who were treated with aspirin or not. The primary endpoint was a composite of major adverse cardiovascular events (MACEs). Secondary endpoints included all-cause death, cardiovascular death and myocardial infarction (MI). The pooled effect size was estimated as hazard ratio (HR) with 95% confidence interval (CI), which was measured by a random effect model using the generic inverse variance method.ResultsThirteen published studies with 34,463 patients were included. Pooled data showed that aspirin therapy was not associated with the risk of MACEs (HR 1.10; 95% CI 0.85–1.41; P = 0.47, I2 = 57%). Similar results were observed in cardiovascular death (HR 1.12; 95% CI 0.73–1.73; P = 0.60, I2 = 0%) and MI (HR 0.53; 95% CI 0.09–3.20; P = 0.49, I2 = 68%), except all-cause death (HR 0.77; 95% CI 0.63–0.95; P = 0.02, I2 = 25%). Subgroup analyses showed that there were no associations between aspirin therapy and MACEs in all subsets.ConclusionsRoutine aspirin therapy might not improve prognosis in patients with nonobstructive CAD. Aspirin therapy in non-obstructive CAD should be better investigated and future research is needed. A personalized antiplatelet regimen might contribute to reduction in ischemic cardiovascular events in patients with non-obstructive CAD.Registration: PROSPERO (CRD42021281706).