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Objective To study indications for penetrating keratoplasty (PK) at a single site. The trends in the causative organisms for infectious keratitis requiring surgery were also evaluated. Design Retrospective observational study. Participants A total of 1181 eyes of 935 patients undergoing PK between January 2000 and December 2015 in Northern Alberta, Canada. Methods Indications for PK were evaluated over the 16-year study period, and the trends in these indications were compared over 5-year intervals. The microbiology of infectious keratitis cases requiring surgery was similarly evaluated. Results The most common indications for PK from 2000 to 2015 were keratoconus (23%), re-graft (22%), and corneal scar (12%). There was a decline in the percent of total surgeries done for Fuchs’ dystrophy (p = 1.1 × 10−3) and pseudophakic bullous keratopathy (p = 5.6 × 10−5), whereas a corresponding increase in keratoconus (p = 3.2 × 10−5), trauma (p = 2.1 × 10−3), and infectious keratitis cases (p = 0.010) was observed. The most common causes for infectious keratitis cases were viral (45%), bacterial (18%), parasitic (11%), and fungal (9%). There was a significant increase in the percent of infectious keratitis cases due to a viral etiology from 2005 to 2010 (p = 6.4 × 10−3). Conclusions The indications for PK are comparable with other centres in North America. Nearly half of all infectious keratitis cases requiring surgery are viral. The increase in viral cases requiring surgery may reflect improved diagnostics or recurrent cases.