Purpose: To compare outcomes of patient who underwent surgery using perfluorooctane (PFO; C8F18; Ala Octa) with those who underwent surgery with perfluorodecalin (F-Decalin). Design: Retrospective, consecutive, comparative, interventional case series. Methods: A total of 48 eyes that underwent vitrectomy with PFO were compared to 29 eyes that underwent vitrectomy with perfluorodecalin. Two experienced surgeons performed vitrectomies at the Geneva University Eye Clinic. Visual acuity before, at 8 and 24 weeks after surgery, was documented, and spectral domain optical coherence tomography (SD-OCT) images were analyzed for abnormalities. Results: Two patients experienced severe retinal toxicity, including 1 with severe vision loss. However, no statistical differences in VA were observed between the PFO and perfluorodecalin patients. Analysis of SD-OCT images showed differences in occurrence of several abnormalities, for example, inner segment-outer segment alterations were found in 60.4% of eyes treated with PFO and in 10.3% of perfluorodecalin-treated eyes; retinal atrophic areas were found in 41.7% of PFO and in none of the perfluorodecalin eyes; inner limiting membrane contraction was found in 58.4% of PFO and in none of perfluorodecalin eyes; inner retina cystic alterations were found in 58.3% of PFO eyes and 17.2% of perfluorodecalin eyes; outer retina cystic alterations were found in 39.6% of PFO eyes and 13.8% of perfluorodecalin eyes; retinal holes were found in 14.6% of PFO eyes and in none of the perfluorodecalin eyes; and outer retinal inclusions were found in 20.8% of PFO eyes and in 3.45% of perfluorodecalin eyes. Conclusions: Perfluorooctane caused significantly more toxic damage than perfluorodecalin. Special consideration should be given to develop a central European Union (EU) control agency for medical devices and to reevaluate safety procedures currently accepted by the EU and International Organization for Standardization for intraocular surgery.