Background: The water-perfusable tissue index (PTI) is assumed to differentiate viable myocardium from scar tissue, but histological comparisons in humans are lacking. The present study compares PTI with delayed contrast-enhanced magnetic resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI threshold for detection of myocardial viability was defined when DCE-MRI was taken as a reference. Materials: Twenty patients with ischemic LV dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and DCE-MRI. Results: Of the 200 analyzed segments, 112 demonstrated DCE and were subsequently divided in three subgroups according to the severity of enhancement. PTI was 1.04 ± 0.21 in control segments and gradually decreased with increasing extent of DCE to 0.77 ± 0.31 for segments with transmural enhancement (p < 0.001). However, PTI progressively underestimated infarct size with increasing quantities of scar tissue (r = 0.61, p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for detection of myocardial viability with sensitivity and specificity values of 75 and 77%, respectively. Conclusions: PTI is inversely related to the extent of scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease and LV dysfunction. However, with increasing quantities of scar tissue, PTI overestimates the extent of residual viable tissue. A PTI threshold of 0.89 yields the best diagnostic accuracy for viability detection.