General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within , and specific wavelength shift was limited to . Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.