Scleral fixation and iris fixation are common intraocular lens (IOL) implantation techniques performed because of zonulopathy. There is a lack of consensus regarding their comparative efficacy and safety. This study aims to compare the efficacy and safety outcomes after scleral-fixated (SF) vs iris-fixated (IF) IOL implantation or fixation in adults. A systematic literature search was conducted on Ovid MEDLINE, Embase, and Cochrane CENTRAL from 2005 to 2020. 785 eyes from 2 randomized controlled trials and 9 nonrandomized studies were included. There was no significant difference in the mean corrected distance visual acuity at the final follow-up (P = .52) or absolute change in spherical equivalent (P = .88) between SF IOL and IF IOL implantation. The incidence of vitreous hemorrhage was significantly higher in the SF IOL group (risk ratio = 3.66, 95% CI, 1.16-11.55, P = .03). There were no differences in visual acuity and refractive outcomes between SF IOL and IF IOL implantation or fixation. Trade-offs in complications exist between the 2 techniques.