Introduction: To evaluate the safety and efficacy of new-generation hybrid contact lenses (HCL) among patients with irregular astigmatism. Methods: Medical records of 25 patients fit with new-generation HCL (Eyebrid(R)and AirFlex(R)) were retrospectively reviewed. The data collected included etiology of irregular astigmatism, uncorrected visual acuity, manifest refraction, spectacle-corrected visual acuity (S-CDVA), steep / flat keratometric values, corneal astigmatism, records of rigid / soft CL fitted before HCL, all parameters of the trial lenses, and the final prescribed HCL parameters and HCL-CDVA. Results: The study included 34 eyes from 25 patients (nine females and 16 males) with an average age of 29 +/- 13 (ranging from 8-56) years. In total, 25 eyes with keratoconus, four with post - keratoplasty astigmatism, three with irregular astigmatism due to corneal trauma and two with residual astigmatism after radial keratotomy were fit with HCL. The mean S-CDVA (logMAR) improved significantly from 0.76 +/- 0.41 to 0.14 +/- 0.15 with HCL (p< 0.01). The most common indication for HCL was inability to fit with rigid gas permeable (RGP) lenses (22 eyes). The average number of lenses to successful fit was 1.4 (mode, 1; median, 1) and ideal fit was achieved with the first trial lens in 25 eyes (73%). Seven patients (nine eyes, 36%) discontinued lens use within the first 6 months because of discomfort (six eyes, 24%), ocular allergy (two eyes, 8%) and tearing of contact lens (one eye, 4%). Discussion: New-generation HCL may be a suitable option for fitting challenging corneas with irregular astigmatism that cannot be rehabilitated efficiently with rigid lenses.