To evaluate femtosecond laser lens fragmentation and anterior capsulotomy in cataract surgery. Anterior capsulotomy and phacofragmentation procedures performed with an intraocular femtosecond laser (LenSx Lasers Inc) were initially evaluated in ex vivo porcine eyes. These procedures were then performed in an initial series of nine patients undergoing cataract surgery. In addition to standard intraoperative assessments (including capsulotomy diameter accuracy and reproducibility), optical coherence tomography was used to evaluate human procedures. For an intended 5-mm capsulorrhexis in porcine eyes, average achieved diameters were 5.88+/-0.73 mm using a standard manual technique and 5.02+/-0.04 mm using the femtosecond laser. Scanning electron microscopy revealed equally smooth cut edges of the capsulotomy with the femtosecond laser and manual technique. Compared to control porcine eyes, femtosecond laser phacofragmentation resulted in a 43% reduction in phacoemulsification power and a 51% decrease in phacoemulsification time. In a small series of human clinical procedures, femtosecond laser capsulotomies and phacofragmentation demonstrated similarly high levels of accuracy and effectiveness, with no operative complications. Initial results with an intraocular femtosecond laser demonstrate higher precision of capsulorrhexis and reduced phacoemulsification power in porcine and human eyes.