We describe the case of an 86-year-old patient, pseudophakic in both eyes and with high myopia, who had previously had a 25-G vitrectomy with 20% C3F8 used as a tamponade due to a total retinal detachment with choroidal hemorrhages and macular hole. At the postoperative 4-month follow-up, we found 360° iridocorneal synechiae with elevated intraocular pressure due to angle closure in all sectors, with an adherent retina and in the absence of choroidal hemorrhage/detachment and of corneal edema or endothelial damage. The patient was, therefore, hospitalized to receive 360° anterior synechiolysis with a single opening to the corneal limbus, like in paracentesis, with topical anesthesia. We have tried to study the possible causes of this case history. However, it should be recognized that the development of iridocorneal synechiae and the rise of intraocular pressure can be a possible complication of air/C3F8 vitrectomy, which cannot be managed with medical therapy. It will be essential to monitor the situation and to hospitalize the patient for surgical synechiolysis to restore the normal anatomy and physiology and to correct the ocular hypertension. During the vitrectomy, we will have to introduce in advance an adequate amount of viscoelastic material in the anterior chamber and to perform a preventive surgical iridectomy, even if the iridocorneal angle is open in all sectors.