Abstract Aims T1 mapping reactivity (ΔT1) has been proposed as a novel contrast-free technique to detect obstructive coronary artery disease (CAD). The aims of the study are: 1) to compare the cardiovascular magnetic resonance (CMR)-derived ΔT1 with quantitative perfusion (QP CMR) measures; 2) to assess the influence of sex and comorbidities on ΔT1; and 3) to assess the diagnostic accuracy of ΔT1 to detect obstructive CAD diagnosed with the invasive coronary angiography (ICA) and/or fractional flow reserve. Methods and results This study retrospectively analyzed 51 patients with suspected obstructive CAD who underwent CMR including rest and adenosine stress first-pass perfusion and native T1 mapping (MOLLI). A moderate correlation was found between pooled rest and stress native T1 mapping and MBF (Pearson’s r=0.476; p<0.001). When stratified by MPR, ischemic myocardium had significantly lower stress T1 mapping values (p<0.001) and ΔT1 (p=0.005) vs. nonischemic myocardium. Male sex and history of diabetes were independently associated with lower ΔT1. The optimal cut-off value of Δ T1 to detect impaired MPR on a per-vessel basis was ≤5.4%, with an AUC of 0.662 (95% CI: 0.563-0.752, p=0.003), sensitivity of 84% (95% CI: 67-95) and specificity of 46% (95% CI: 34-58). When validated against ICA, stress T1 and Δ T1 did not reach statistical significance in detecting obstructive CAD. Conclusion ΔT1 is significantly influenced by sex and comorbidities and has poor diagnostic accuracy for detecting myocardial ischemia. Therefore, the clinical utility of ΔT1 in a real-world cohort of patients to detect obstructive CAD is limited.