Although　fractional　flow　reserve　(FFR)　and　coronary　flow　reserve　(CFR)　are　both　frequently　used　to　assess　the　functional　severity　of　coronary　artery　stenosis,　discordant　results　of　diagnosis　between　FFR　and　CFR　in　some　patient　cohorts　have　been　reported.　In　the　present　study,　a　computational　model　was　employed　to　quantify　the　impacts　of　various　pathophysiological　factors　on　FFR　and　CFR.　In　addition,　a　hyperemic　myocardial　ischemic　index　(HMIx)　was　proposed　as　a　reference　for　comparing　the　diagnostic　performances　of　FFR　and　CFR.　Obtained　results　showed　that　CFR　was　more　susceptible　than　FFR　to　the　influence　of　many　pathophysiological　factors　unrelated　to　coronary　artery　stenosis.　In　particular,　the　numerical　study　proved　that　increasing　hyperemic　coronary　microvascular　resistance　significantly　elevated　FFR　while　reducing　CFR　despite　fixed　severity　of　coronary　artery　stenosis,　whereas　introducing　aortic　valve　disease　only　caused　a　significant　decrease　in　CFR　with　little　influence　on　FFR.　These　results　provided　theoretical　evidence　for　explaining　some　clinical　observations,　such　as　the　increased　risk　of　discordant　diagnostic　results　between　FFR　and　CFR　in　patients　with　increased　hyperemic　microvascular　resistance,　and　significant　increase　in　CFR　after　surgical　relief　of　severe　aortic　valve　disease.　When　evaluated　with　respect　to　the　predictive　value　for　hyperemic　myocardial　ischemia,　the　performance　of　FFR　was　found　to　be　considerably　compromised　in　the　presence　of　severe　coronary　vasodilation　dysfunction　or　aortic　valve　disease,　whereas　the　relationship　between　CFR　and　HMIx　remained　relatively　stable,　suggesting　that　CFR　may　be　a　more　reliable　indicator　of　myocardial　ischemia　under　complex　pathophysiological　conditions.　©　2019　John　Wiley　&　Sons,　Ltd.