Purpose: To evaluate the visual and corneal outcomes of new generation hybrid contact lenses (HCL) in patients with advanced keratoconus. Methods: This was a retrospective study undertaken at a single academic center. The study cohort consisted of subjects with advanced keratoconus who had elected not to undergo keratoplasty and were fitted with HCLs. Patients were fitted either with EyeBrid (LCS, Cane, France) or Airflex (SwissLens, Prilly, Switzerland) HCLs. Primary outcome measures included contact lens (CL) drop-out rate, best corrected visual acuity, and corneal endothelial cell density (ECD) measurements at the end of a 6-month HCL wear. ECD was measured using in vivo confocal microscopy (ConfoScan4; Nidek, Tokyo, Japan). One eye per patient was included for statistical purposes. Pairedttests and Wilcoxon signed-rank tests were used for comparative analyses. Results: Thirty-two keratoconic eyes of 32 patients (14M/18F) with a mean age of 25.9 +/- 11.5 years were included in the study. All patients were able to continue CL wear for a duration of 6 months. There was a significant improvement in the mean best corrected visual acuity from 0.5 +/- 0.2 logarithm of minimal angle of resolution to 0.1 +/- 0.1 logarithm of minimal angle of resolution after daily CL wear with HCL at the 6-month follow-up visit (P< 0.001). No vision-threatening CL-related corneal adverse effects were observed. There was no significant reduction in the ECD noted at the 6-month visit [2625.8 +/- 300.3 cells/mm(2)(baseline) vs. 2566.4 +/- 309.8 cells/mm(2)(6-month);P= 0.623]. Conclusions: Hybrid contact lenses can provide improved visual function without inducing any short-term clinical or microscopic adverse effects on corneal endothelial cells in patients with advanced keratoconus.