Purpose: To evaluate the outcome of posterior capsule opacification (PCO) after implantation in rabbit eyes of currently available 3-piece and 1-piece hydrophobic acrylic intraocular lenses (IOLs) with square optic edges. Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Methods: The 3-piece designs evaluated were the AR40e (Advanced Medical Optics Inc.) and the MA60AC (Alcon, Inc.); the 1-piece designs were the SA60AT and the SA30AT (Alcon, Inc.). Nine lenses of each type were implanted in a randomized manner by the same surgeon in 18 Dutch Belted pigmented rabbits. After a follow-up of 3 weeks, the rabbits were killed and analyses of the enucleated eyes were performed from the posterior or Miyake-Apple view. The intensity of central PCO, peripheral PCO, and Soemmering's ring formation was scored from 0 to 4. The area of Soemmering's ring formation was also scored from 0 to 4 based on the number of quadrants involved. Other parameters analyzed were capsulorhexis coverage of the IOL anterior surface, IOL centration, fixation, and presence of striae. Results from the posterior view were complemented by histopathologic evaluation of the eyes. Results: No statistically significant difference was found between the 4 groups of IOLs in the parameters analyzed from the posterior view. When cell ingrowth occurred with the 1-piece designs, causing peripheral and central PCO formation, it was more likely to start at the optic-haptic junctions, as observed during the clinical follow-up with slitlamp examination and confirmed by gross and histopathologic analyses of the enucleated eyes. Conclusions: The square, truncated optic edge is the most important IOL design feature for PCO prevention. The optic-haptic junctions of the 1-piece designs appear to be sites where the barrier effect of the truncated optic edge is less effective.