The Medina classification is used to determine the presence of significant stenosis (≥50%) within each of the 3 arterial segments of coronary bifurcation in invasive coronary angiography (ICA). The utility of coronary computed tomography angiography (coronary CTA) for assessment of Medina classification is unknown. We aimed to compare the agreement and reproducibility of Medina classification between ICA and coronary CTA, and evaluate its ability to predict side branch (SB) occlusion following percutaneous coronary intervention (PCI). In total 363 patients with 400 bifurcations were included, and 28 (7%) SB occlusions among 26 patients were noted. Total agreement between CTA and ICA for assessment of Medina class was poor (kappa = 0.189), and discordance between both modalities was noted in 253 (63.3%) lesions. Larger diameter ratio between main vessel and SB in CTA, and larger bifurcation angle in ICA were independently associated with discordant Medina assessment. Whereas the interobserver agreement on Medina classification in CTA was moderate (kappa = 0.557), only fair agreement (kappa = 0.346) was observed for ICA. Finally, Medina class with any proximal involvement of main vessel and SB (1.X.1) on CTA or ICA was the most predictive of SB occlusion following PCI with no significant differences between both modalities (area under the curve 0.686 vs 0.663, p = 0.693, respectively). In conclusion, Medina classification was significantly affected by the imaging modality, and coronary CTA improved reproducibility of Medina classification compared with ICA. Both CTA and ICA-derived Medina class with any involvement of the proximal main vessel and SB was predictive of SB occlusion following PCI.