Intraocular lens (IOL) design, optical configuration, and placement have potential effects on postoperative outcome. Laboratory studies have suggested that one-piece, biconvex designs may reduce or delay posterior capsular opacification and that in-the-bag fixation of the posterior chamber IOL may reduce inflammation. To document the clinical significance of IOL design and placement, we conducted a randomized, prospective, clinical trial. Six hundred uncomplicated capsulorhexis and phacoemulsification patients were randomized in a three-factor design to receive an IOL that was one-piece or three-piece, had a biconvex, plano-convex, or laser ridge optic, and was bag-or sulcus-fixated. Treatment differences were related to lens placement. Patients with bag-fixated IOLs had less posterior capsular opacification, fewer YAG laser capsulotomies, a higher percentage of centered lenses, less inflammation, and fewer late posterior capsular striae than those with sulcus-fixated IOLs. In the latter group, patients with three-piece IOLs had fewer posterior capsular striae at three months postoperatively. All six occurrences of haptic loop distortion were in patients with three-piece IOLs. Patients with the one-piece design had less late inflammation than those with the three-piece design. Fewer YAG capsulotomies were necessary at one year in patients with the biconvex design than in those with the plano-convex or laser ridge configurations. Operative complications, endothelial cell loss, and postoperative complications were not IOL-related.