Our precise in vivo investigations examined various laser choices for TMR including Ho:YAG, CO2 and XeCl excimer laser. These studies have revealed that among the three lasers tested, the XeCl excimer ablation produces the least tissue damage. In this study we have further examined the use of the excimer laser for optical application in TMR. To this end, myocardial ablation was conducted in vivo in a porcine model with the use of multiple fiber catheters of 1.0mm and 1.4mm in diameter. During ablation, the catheters were advanced into the myocardium at different constant speeds via a specially designed electromechanical device. Each of the catheters was tested at 35 mJ/mm2 and different pulse repetition rate. Optimal operating parameters were defined as those that produced the most uniform tissue ablation, and the least thermal and shock- wave damage as determined via computerized histopathological analysis. We have found that ablation rate, pulse repetition rate, catheter size, and catheter advancement speed are parameters closely intertwined and crucial to the histological outcome of TMR. Within the values of parameters tested, larger catheters, pulse repetition rates between 35 and 40 Hz, and advancement speeds of about 1.3 mm/s (~0.05 inches/s) seem to provide reasonably optimized parameters for excimer-based TMLR.