Abstract: Immunosuppressive therapy is the main postoperative treatment for keratoplasty, but there are considerable differences in protocols for the use of steroids and other immunosuppressants. Therefore, we conducted 2 prospective randomized clinical trials and 1 prospective nonrandomized clinical trial on keratoplasty postoperative treatment. One study evaluated the efficacy and safety of long-term topical corticosteroids after a penetrating keratoplasty was performed. Patients who underwent keratoplasty and maintained graft clarity for >1 year were randomly assigned to either a steroid or a no-steroid group. At the 12-month follow-up, the no-steroid group developed significantly more endothelial rejection than did the steroid group. A second study elucidated the effectiveness and safety of systemic cyclosporine in high-risk corneal transplantation. The patients were assigned to a systemic cyclosporine or control group. At a mean follow-up of 42.7 months, no difference was observed in the endothelial rejection rates and graft clarity loss between the 2 groups. A third study elucidated the effectiveness and the safety of systemic tacrolimus in high-risk corneal transplantation. Of 11 consecutive eyes decompensated despite systemic cyclosporine treatment, there was no irreversible rejection in eyes treated with tacrolimus, which was significantly better than in previous penetrating keratoplasty with systemic cyclosporine treatment. Prognosis after keratoplasty in patients with keratoconus is relatively good, but special attention is required for patients with atopic dermatitis. Postkeratoplasty atopic sclerokeratitis (PKAS) is a severe form of sclerokeratitis after keratoplasty in atopic patients. Our retrospective study showed that 35 eyes of 29 patients from a total of 247 keratoconus eyes undergoing keratoplasty were associated with atopic dermatitis, of which 6 eyes of 5 patients developed PKAS. Eyes with PKAS had a significantly higher incidence of atopic blepharitis and preoperative corneal neovascularization, and therefore, we suggest systemic corticosteroids or cyclosporine to prevent PKAS in such high-risk cases.