Abstract Background The index of microcirculatory resistance (IMR) has been widely used for the assessment of microcirculatory function and the detection of the territory with microvascular dysfunction. For measuring coronary physiological indices including IMR, a pressure/temperature sensor-tipped guidewire is recommended to be located distally to the target lesion, however the determinants of IMR including wire location other than the hyperemic microvascular resistance itself are still undetermined. Purpose This study aimed to clarify the determining factors including coronary computed tomography angiography (CCTA) findings, wire position and vessel anatomy and its effect on IMR values. Methods We retrospectively investigated 121 intermediate left anterior descending artery lesions in chronic coronary syndrome patients in our institutional physiological registry (July 2020 to Aug 2022). All patients underwent preprocedural CCTA and coronary physiological assessment with pressure/temperature sensor-tipped guidewire during invasive coronary angiography or percutaneous coronary intervention (PCI). We placed the wire as far distal as practical for the assessment of physiological indices. Under adenosine-induced hyperemia, the wire was pulled manually to the guide catheter and its pullback length was recorded. CCTA assessment included qualitative lesion morphology assessment (spotty calcification, low attenuation plaque, napkin ring sign) and quantitative plaque analysis (remodeling index). Epicardial fat volume is also measured with the proprietary semi-automated software. The predicting factors for IMR was investigated. Result In a total cohort, IMR was 20.40 (14.07-29.92), and the prevalence of IMR>25 was 36 %. On linear regression analysis, patient characteristics including age and gender were not significant predictors for IMR. CCTA-based high risk plaque features (Spotty calcification, low attenuation plaque and napkin ring sign) were also not associated with IMR. In univariable and multivariable linear regression analysis, wire pullback length, remodeling index and epicardial fat volume were significant predictors for IMR (β 1.369 [0.223-2.515, p=0.020, β 6.651 [1.486-11.815], p=0.012, and β 0.055 [0.008-0.103], p=0.023, respectively). Conclusion Wire location (length form the coronary ostium), remodeling index and epicardial fat volume affects IMR values. Caution should be exercised for the interpretation of IMR values in consideration of these factors.