Purpose: To assess the role of femtosecond laser-assisted capsulotomy centration in the long-term intraocular positioning of a multifocal intraocular lens. Design: Prospective comparative study. Methods: A total of 60 eyes of 30 patients underwent femtosecond laser–assisted Refractive Lens Exchange (RLE). For every patient, capsulotomy centration was randomly performed according to pupil centre (PC) in one eye and first Purkinje reflex (FPR) in the other. The intraocular lens (IOL) positioning, visual acuities, spherical equivalent, internal aberrometry and quality of vision were assessed and compared at 3 years’ follow-up between groups (PC and FPR). Results: Intraocular lens positioning showed a statistically significant difference between groups, with a closer centration to the visual axis in the FPR patients (p=<0.001). Internal aberrometry showed higher values in the PC capsulotomy centration group (p<0.01). Conclusions: First Purkinje reflex (FPR) centered capsulotomy is associated to a closer centration of the IOL to the visual axis.