OBJECTIVE The purpose of this study is to compare photocoagulation with the argon green, krypton red, and diode infrared laser indirect ophthalmoscopes in an experimental setting. METHODS Photocoagulation was performed with each of the laser indirect ophthalmoscopes in a grid pattern within one sector of the same eye of 14 Dutch-belted rabbits. Treatment was performed either with or without scleral depression. Measurements of the retinal burn diameters were performed after hemisecting the globes, and the burns were examined with light microscopy. RESULTS Variation in burn intensity and diameter (10% to 28%) was common with all 3 laser indirect ophthalmoscopes. Five times more output energy was required to make equivalent burns with the diode laser indirect ophthalmoscope than with the argon or krypton laser indirect ophthalmoscopes. Choriovitreal hemorrhages only occurred during scleral depression. Histopathologically, the argon green laser indirect ophthalmoscope burns spared the choroid and inner sclera, while the intense krypton and diode burns had full-thickness choroidal involvement and even thermal injury to the inner sclera. Scleral depression reduced the mean energy required to create equivalent burns with all three laser indirect ophthalmoscopes. There was a 10% to 40% reduction in the mean retinal burn diameter with scleral depression (argon green, P < 0.0005; krypton red, P < 0.0005; and diode, P < 0.025). CONCLUSIONS Photocoagulation with the argon green, krypton red, or diode infrared laser indirect ophthalmoscopes is a safe and effective method of retinal ablation. Decreasing the posterior nodal distance of the eye with scleral depression will produce a smaller spot on the retina with the laser indirect ophthalmoscope.