Introduction: Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated.Hypothesis: We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain.Methods: We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders.Results: 2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p<0.001). To rule out the impact of potential confounders, we performed a multivariable analysis adjusting for potential risk factors for re-hospitalization, including age, BMI, hypertension, dyslipidemia, diabetes, smoking, and creatinine; this analysis confirmed the significant association of admission SHR and re-hospitalization in INOCA patients.Conclusions: To the best of our knowledge, this is the first report showing that admission SHR is an independent risk factor for hospitalization in INOCA patients, with or without diabetes. Our data indicate that hyperglycemia may trigger coronary microvascular dysfunction driving worse outcomes in this class of patients; in this context, glycemic control may be a main goal to be achieved in this population. Further studies in larger populations and with a longer follow-up are warranted to confirm our findings.