To comparatively evaluate the clinical and microbiological profiles and treatment outcome of cases with post-penetrating keratoplasty (PK) infectious keratitis in failed and clear grafts.Retrospective, matched cohort study.All cases of infectious keratitis following penetrating keratoplasty admitted to the Royal Victorian Eye and Ear Hospital, Melbourne, between January 1998 and December 2008 were identified through a retrospective medical chart review. Cases without any surface sutures were selected and divided into 2 groups, microbial keratitis with pre-existing graft failure and microbial keratitis in clear graft on presentation. Demographic, clinical, and microbiological profiles of cases in both groups were analyzed and compared.Patients in the failed-graft group were older (P = .004) and had an early onset of graft infection (P = .049), compared with patients in the clear-graft group. All patients in the failed-graft group were on long-term corticosteroid drops at the time of presentation (vs 76% in clear-graft group; P = .005). Moraxella sp was more frequently isolated in the failed-graft group (30.4%) compared with the clear-graft group (8%). A higher number of cases in the clear-graft group required surgical intervention in the form of corneal gluing and therapeutic corneal transplantation compared with the failed-graft group (P = .03).Prolonged use of corticosteroid eye drops is a major risk factor for the occurrence of postkeratoplasty infectious keratitis in failed and clear grafts. Infections in failed grafts occur earlier as compared to clear grafts, and indolent organisms like Moraxella are prevalent in patients with failed grafts in Australia.