(1)　Background:　Arrhythmia,　which　is　an　umbrella　term　for　various　types　of　abnormal　rhythms　of　heartbeat,　has　a　high　prevalence　in　both　the　general　population　and　patients　with　coronary　artery　disease.　So　far,　it　remains　unclear　how　different　types　of　arrhythmia　would　affect　myocardial　perfusion　and　the　risk/severity　of　myocardial　ischemia.　(2)　Methods:　A　computational　model　of　the　coronary　circulation　coupled　to　the　global　cardiovascular　system　was　employed　to　quantify　the　impacts　of　arrhythmia　and　its　combination　with　coronary　artery　disease　on　myocardial　perfusion.　Furthermore,　a　myocardial　supply-demand　balance　index　(MSDBx)　was　proposed　to　quantitatively　evaluate　the　severity　of　myocardial　ischemia　under　various　arrhythmic　conditions.　(3)　Results:　Tachycardia　and　severe　irregularity　of　heart　rates　(HRs)　depressed　myocardial　perfusion　and　increased　the　risk　of　subendocardial　ischemia　(evaluated　by　MSDBx),　whereas　lowering　HR　improved　myocardial　perfusion.　The　presence　of　a　moderate　to　severe　coronary　artery　stenosis　considerably　augmented　the　sensitivity　of　MSDBx　to　arrhythmia.　Further　data　analyses　revealed　that　arrhythmia　induced　myocardial　ischemia　mainly　via　reducing　the　amount　of　coronary　artery　blood　flow　in　each　individual　cardiac　cycle　rather　than　increasing　the　metabolic　demand　of　the　myocardium　(measured　by　the　left　ventricular　pressure-volume　area).　(4)　Conclusions:　Both　tachycardia　and　irregular　heartbeat　tend　to　increase　the　risk　of　myocardial　ischemia,　especially　in　the　subendocardium,　and　the　effects　can　be　further　enhanced　by　concomitant　existence　of　coronary　artery　disease.　In　contrast,　properly　lowering　HR　using　drugs　like　beta-blockers　may　improve　myocardial　perfusion,　thereby　preventing　or　relieving　myocardial　ischemia　in　patients　with　coronary　artery　disease.