PURPOSE: To evaluate and compare the effects of femtosecond laser-assisted anterior capsulotomy and manual anterior capsulorhexis on posterior capsule opacification (PCO) development. METHODS: Femtosecond laser-assisted anterior capsulotomy was performed in 40 eyes of 40 patients (FS group) and manual anterior capsulorhexis was performed in 39 eyes of 39 patients (CCC group). An AcrySof one-piece hydrophobic acrylic intraocular lens (Alcon Laboratories, Inc., Fort Worth, TX) was implanted in all eyes. The PCO level was measured using Open-Access Systematic Capsule Assessment (OSCA) software 18 to 26 months after surgery. Postoperative intraocular lens position (ie, tilt and decentration) was measured using Scheimpflug images (Pentacam; Oculus Optikger te GmbH, Wetzlar, Germany). RESULTS: There was no statistically significant difference in age, axial length, and follow-up time between the two groups (P > .05). Vertical tilt, horizontal and total decentration of intraocular lenses, and PCO proved to be significantly higher in the CCC group (P = .03, .04, .03, and .01, respectively). After adjusting for axial length and follow-up time, manual anterior capsulorhexis was found to be a significant predictor of higher PCO scores in the multivariable regression model (beta: 0.33; 95% CI: 0.01 to 0.65; P = .04). Vertical tilt affected PCO scores after adjusting for axial length and follow-up time (beta: 0.07; 95% CI: 0.01 to 0.12; P = .02). No capsulotomies were performed during follow-up in either group. CONCLUSIONS: Femtosecond laser-assisted anterior capsulotomy proved to be a safe procedure for postoperative PCO rates. Due to better intraocular lens position, femtosecond laser-assisted anterior capsulotomy resulted in slightly decreased PCO scores; however, evaluating its clinical significance requires further studies.