Abstract Background In patients with angina and no obstructive coronary disease (ANOCA), the underlying pathophysiology includes microvascular angina (endothelial-dependent and independent coronary microvascular dysfunction (CMD)) and vasospastic angina (microvascular spasm and epicardial spasm) diagnosed with invasive coronary functional angiography (CFA). However, whether there are differences in demographics, clinical characteristics, and outcomes by underlying diagnosis is unknown. We hypothesize that microvascular angina patients will be older and have more cardiovascular risk factors and worse outcomes than the vasospastic angina group. Objective To explore the differences in demographics, risk factors, and outcomes in ANOCA patients with microvascular and vasospastic angina. Methods A prospective registry-based cohort study of consecutive CFA was performed in 156 ANOCA patients between 2020 and 2023 using the Doppler-tipped guide wire method. Patients were classified into microvascular angina, vasospastic angina, and mixed disease. Microvascular angina was defined as endothelial-independent CMD (coronary flow reserve [CFR] < 2.5 in response to adenosine) and/or endothelial-independent CMD (coronary blood flow [CBF] < 50% or no change in vessel diameter in response to 54 mcg intracoronary acetylcholine). Vasospastic angina as microvascular (<90% constriction) and epicardial spasm (>90% constriction) to 108 mcg intracoronary acetylcholine. The mixed disease group included microvascular and vasospastic angina. Validated questionnaires evaluated angina (SAQ-7), functional capacity (DASI), dyspnea severity (UCSD SOB), and perceived stress (PSS) were obtained from patients at office visits prior to undergoing CFA. Results Among 156 ANOCA patients, 114 had microvascular angina, 10 had vasospastic angina, and 32 had mixed disease. The average age was 58.5 (SD 11.2) years. Demographics and prevalence of risk factors, such as hypertension, hyperlipidemia, or diabetes, showed no significant differences among the microvascular, vasospastic, or mixed disease groups. The prevalence of heart failure with preserved ejection fraction (HFpEF) was high across the groups, and outcomes did not differ significantly among them. The SAQ-7 score average ranged from 16.9 to 40.3, consistent with moderate to severe angina, and the DASI score ranged from 32.2 to 34.9, consistent with moderate functional capacity. Dyspnea severity ranged from 30 to 41, consistent with low to moderate severity, and perceived stress ranged from 11.5 to 13, consistent with low to moderate stress among all participants. Conclusion In patients with ANOCA undergoing invasive CFA, demographics, cardiovascular risk factors, and outcomes were similar regardless of underlying diagnosis. We demonstrate a high prevalence of risk factors and HFpEF and evidence of moderate to severe symptoms and functional capacity in ANOCA patients across all diagnoses.Abbreviation explanation for table 1