Purpose: The examination of the effects of second generation lotrafilcon B silicone hydrogel (SiH) lenses on the cornea when worn for three years of daily wear. Material and Methods: 55 healthy patients were divided into two groups: current hydrogel contact lens wearers refitted with lotrafilcon B lenses (Group 1; 28 patients) and neophyte contact lens wearers (Group 2; 27 patients). Each patient's subjective eye comfort was measured with a self-administered questionnaire. The corneas were analyzed using contact specular microscope to measure corneal thickness and the endothelium before the SiH lenses were fitted after four weeks, one month, six months, one year, two years, and three years of lens wear. Results: Subjective complaints of patients in Group 1 were reduced; however patients in Group 2 experienced discomfort during the first two to four weeks of use. In Group 1, objective examinations identified a decrease in endothelial cell density. In Group 2, the endothelial cell density increased slightly in the first two years but decreased after three years. The results indicate that lotrafilcon B slows down the deleterious effects of contact lenses. The coefficient of variation significantly decreased after six months in Group 1 (0.47 vs 0.44; p = 0.049), whereas, in Group 2, the hexagonal cells improved significantly after one month (27.78 vs 28.25; p = 0.025). Conclusion: Based on the subjects involved and the period of time under examination, it can be concluded that high-Dk SiH lenses support the physiological metabolism and functions of the cornea by improving oxygen provision.