PURPOSE: To evaluate the effect of genipin, a natural crosslinker, on porcine corneas. SETTING: Department of Ophthalmology, Universidad Nacional de Colombia, Bogota, Colombia. METHODS: Corneal strips (12.0 mm × 2.3 mm) were harvested from porcine eyes and treated by incubation with genipin at concentrations of 1.00%, 0.25%, and 0.10%. Parallel corneal strips from the same eye were used as untreated controls. After treatment at 20°C for 40 minutes, tensile strain measurements were performed in a biomaterial tester. Porcine button corneas were treated with genipin 0.25% for 15 minutes and then digested by bacterial collagenase. Treated and untreated corneas were evaluated by light microscopy. RESULTS: Young modulus and stiffness in treated corneas increased in a concentration-dependent manner. Genipin increased resistance to corneal collagenase 5-fold in comparison with the controls. A decrease in the interlamellar space in treated corneas was also observed. CONCLUSIONS: Corneal collagen crosslinking induced with genipin produced a significant increase in biomechanical strength and resistance to bacterial collagenase. This crosslinker could be useful in treating corneal ectasia and corneal infectious and noninfectious diseases involving corneal melting. Financial Disclosure: Neither author has a financial or proprietary interest in any material or method mentioned.