New corneal cross-linking (CXL) devices are capable of using higher UV-A light irradiances than used in original CXL protocols. The Bunsen-Roscoe law states that a photochemical reaction should stay constant if the delivered total energy is kept constant; however, little clinical data are available to support this hypothesis. We investigated the biomechanical properties of four groups (n = 50 each) of porcine corneas. Three groups were exposed to riboflavin 0.1 % and UV-A irradiation of equal total energy (3 mW/cm(2) for 30 minutes, 9 mW/cm(2) for 10 minutes, and 18 mW/cm(2) for 5 minutes). Controls were exposed to riboflavin 0.1% without irradiation. Young's modulus of 5-mm wide corneal strips was used as an indicator of corneal stiffness. We observed a decreased stiffening effect with increasing UV-A intensity. Young's modulus at 10% strain showed significant differences between 3 mW/cm(2) and 9 mW/cm(2) (P = 0.002), 3 mW/cm(2) and 18 mW/cm(2) (P = 0.0002), 3 mW/cm(2) and the control group (P < 0.0001), and 9 mW/cm(2) and the control group (P = 0.015). There was no difference between 18 mW/cm(2) and the control group (P = 0.064) and between 9 mW/cm(2) and 18 mW/cm(2) (P = 0.503). The biomechanical effect of CXL decreased significantly when using high irradiance/short irradiation time settings. Intrastromal oxygen diffusion capacity and increased oxygen consumption associated with higher irradiances may be a limiting factor leading to reduced treatment efficiency. Our results regarding the efficiency of high-irradiance collagen cross-linking (CXL) raise concerns about the clinical efficiency of the new high-irradiance CXL devices already used in clinical practice without proper validation.