Purpose.To determine the leading indications for penetrating keratoplasty and to identify changing trends in these indications during the past 12 years.Methods.We retrospectively performed a chart review of the hospital records of all patients undergoing penetrating keratoplasty at the National Taiwan University Hospital during a 12-year period (1987–1999). When possible, the clinical indication was corroborated by the pathologic report.Results.A total of 770 corneal transplants were performed. The leading indications for penetrating keratoplasty, in order of decreasing frequency, were corneal scars (27.9%), regraft (21.0%), acute necrotizing and ulcerative keratitis (17.9%), pseudophakic or aphakic bullous keratopathy (17.6%), Fuchs' dystrophy (4.5%), and keratoconus (2.5%). A trend of increasing frequency of regraft and acute necrotizing and ulcerative keratitis, a decreasing frequency of corneal scar, and an initially decreasing then increasing frequency of pseudophakic and aphakic bullous keratopathy were found during the 12-year study period. Acute necrotizing and ulcerative keratitis was found to be the most frequent indication for regraft.Conclusion.In this series, corneal scars, regraft, and acute necrotizing and ulcerative keratitis were the leading indications for penetrating keratoplasty. A changing incidence of pseudophakic and aphakic bullous keratopathy noted during the study period was related to the type of intraocular lens implanted and the method of cataract surgery performed. This study found a comparatively high frequency of acute necrotizing and ulcerative keratitis and an extremely low frequency of keratoconus compared with previous reports.