Objective. The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium. Methods. In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 ( n = 7) received one and in laser group 2 ( n = 7) two laser channels per cm2 in the left anterior descending artery territory. Animals of the ischemic group ( n = 6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed. Results. Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39±0.13 versus 0.14±0.12 ml/min/g; P = 0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups ( P = ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWImax values compared to the ischemic (1.33±0.19 versus 0.93±0.16 mJ/kg; P = 0.03) and laser group 2 (1.33±0.19 versus 1.02±0.15; P = 0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33±46.42, P = 0.029 and 100% versus 116.26±21.06, P = 0.034; respectively). In contrast, the corresponding ischemic group values were not different from intial values ( P = ns). Conclusions. This model of chronic regional ischemia demonstrates that CO2-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.