Purpose: To determine through safety studies the tissue effects and potential cataractogenesis of laser modification of the crystalline lens (photophaco modulation). Setting: Laser Zentrum Hannover, Hannover, Germany. Methods: Six fresh porcine lenses and 6 living rabbit eyes (with the contralateral eye as a control) were radiated with a low-energy femtosecond laser to induce lens fiber disruption. After 3 months, the rabbit eyes were extracted and tested for light scatter and lens function and fixed for histology and ultrastructure. Results: After laser treatment, all lenses displayed a tightly packed array of intralenticular bubbles, which resolved with time. In the porcine eyes, the bubbles coalesced unless spacing of 9 μm or greater was applied at an energy of 2 μJ. In the rabbit eyes, an energy of 1 μJ and spacing of 10 μm was chosen for transcorneal delivery, showing minimum bubble coalescence. After 3 months, the rabbit lenses showed good transparency, with only 1 rabbit having cataract formation unrelated to the laser. Laser scanning studies show essentially identical values for the back focal length and sharpness of focus (variability of back focal length). Ultrastructurally, the rabbit eyes showed a 0.5 μm electron dense border layer with adjacent normal lens architecture. Conclusions: Femtosecond laser photodisruption of the ocular lens yields a self-limited lesion with bubbles that resolve with time. In living animal eyes, no cataract formation was found with no loss of lens function or induced light scatter after 3 months. These results suggest that use of a low-energy femtosecond laser might be safe when modifying the lens for presbyopia correction.