Background: Myocardial ischemia causes accumulation of extracellular myocardial K⁺ ([K⁺]_e). However, the relation between [K⁺]_e, and local coronary venous K⁺, i.e., K⁺ in the great coronary vein ([K⁺]_gcv) has not been established. To determine the sensitivity of [K⁺]_gcv as a marker of myocardial ischemia, we continuously measured [K⁺]_e, using intramyocardial K⁺-selective plunge electrodes, and [K⁺]_gcv, using a catheter-tip K⁺ electrode inserted into the great cardiac vein, during two types of ischemia. Methods and Results: In in-situ pig hearts, ischemia was induced by implementing a progressive decrease in carotid-to-left anterior descending artery (LAD) shunt flow from 40 to 0 mL/min at constant heart rate (100-130/min) and a progressive increase in heart rate from 100 to 160 beats/min at the threshold flow. The progressive decrease in LAD flow to 5 mL/min caused parallel increases in [K⁺]_e (from 3.87 ± 0.37 to 8.65 ± 1.13 mM) and [K⁺]_gcv (from 3.87 ± 0.37 to 4.84 ± 0.43 mM). However, below 5 mL/min, [K⁺]_gcv failed to reflect the increase in [K⁺]_e and often decreased. The progressive increase in heart rate at the threshold flow caused parallel changes in [K⁺]_e (from 4.08 ± 0.36 to 4.87 ± 0.14 mM, n = 3) and [K⁺]_gcv (from 3.08 ± 0.42 to 4.18 ± 0.43 mM). The verapamil- and propranolol-induced changes in [K⁺]_e during low-flow ischemia were reflected by changes in [K⁺]_gcv. Conclusions: Change in [K⁺]_gcv is a sensitive marker of myocardial ischemia, except at very low coronary flow. Thus, [K⁺]_gcv can be used to detect early myocardial ischemia.