Purpose: To evaluate the development of posterior capsule opacification (PCO) after implantation of single-piece hydrophilic acrylic intraocular lenses (IOLs) with an enhanced square edge. Setting: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Methods: The standard 570H Centerflex (Rayner Ltd.) design was compared to 2 new designs with enhanced square edges: the 570E and the 570C. Ten IOLs of each type were implanted in a randomized manner by the same surgeon in 15 pigmented rabbits. After a follow-up of 3 weeks, the rabbits were killed and the eyes were analyzed from the posterior view. The intensity of central PCO, peripheral PCO, and Soemmering's ring formation was graded from 0 to 4. The area of Soemmering's ring was graded from 0 to 4 based on the number of quadrants involved. Other parameters analyzed were capsulorhexis coverage of the IOL edge and IOL centration and fixation. Results from the posterior view were complemented by histopathological evaluation. Results: Posterior capsule opacification was lowest in the 570C group, highest in the 570H group, and intermediate in the 570E group. There was a statistically significant difference between the 3 groups in peripheral PCO (P = .039). No significant difference was found between the groups in the other parameters analyzed. When cell ingrowth occurred with the 570H, it started at the optic-haptic junctions, as observed during the clinical follow-up and confirmed by gross and histopathological analyses. Conclusions: The square optic edge is the most important IOL design feature for PCO prevention. However, it should be present for 360 degrees around the IOL optic to provide an effective barrier effect.