To determine the main causes of intrastromal corneal ring segment (ICRS) explantation and define the incidence rate. Multicenter, observational consecutive case series. Consecutive cases of ICRSs explanted in the last 10 years were reviewed. Clinical data included age of the patients at explantation, reasons for implantation and explantation, date of implantation and explantation, tunnel creation technique, and ICRS type. Main outcomes measures were the reasons for ICRS removal and the incidence rate. During the study period, 121 ICRSs (119 patients) were explanted, with an explantation rate of 5.60%. Functional failure (74 eyes, 61.16%) represents the main cause for ICRS removal: of them, 48 (39.67%) ICRSs were removed for refractive failure and 26 (21.49%) in the setting of a keratoplasty related to poor visual performance of the implanted eye. In addition, 47 eyes (38.84%) had ICRS removal for anatomic failure: among them, 36 (29.75%) were explanted for spontaneous extrusion (overall extrusion rate: 1.58%), 7 (5.79%) for suspected infectious keratitis, 3 (2.48%) for corneal melting, and 1 (0.83%) for corneal perforation. Mild cases of keratoconus were more prone to be explanted because of a loss of the initial improved visual acuity, whereas spontaneous extrusion happened often in advanced cases of keratoconus. We report the largest series of ICRS explantation as of this writing. The main cause of explantation was functional refractive failure followed by spontaneous extrusion of the ICRS, that is, correlated to an anatomic failure at the site of implantation in an advanced disease.