Experiments in dog and rat liver compared the 805-nm wavelength of the diode laser and the 1064-nm wavelength of the Nd:YAG laser. (1) The major optical differences are in the absorption. The optical properties of dog liver were determined by integrating sphere experiments. The scattering coefficients were similar at both wavelengths, but the absorption was 3.5-fold greater for the diode laser wavelength. Consequently, the diode laser penetrated less deeply and heated the liver surface more strongly than the Nd:YAG laser. (2) Blood is a major component of liver absorption. When blood accumulated in the lower region of a rat liver held sideways, surface heating (measured by infrared camera) by the diode laser increased due to increased absorption by the pooled blood. (3) Tissue optics and irradiance geometry together affect the zone of thermal coagulation caused by each laser. The sizes of coagulation lesions in rat liver in vivo indicated larger zones of coagulation with the Nd:YAG laser. Our working hypothesis is that the diode laser caused greater surface heating and water evaporation which means less energy remained in the tissue. Enlarging the spot size of irradiance should alleviate such surface overheating and evaporation losses and maximize the zone of coagulation. The similarities between the two lasers are more striking than the differences.