The microbiological profile of infectious keratitis has shown great differences across the world. Due to the continuous shifting trends in microbiological profile and antibiotic resistance patterns reported in several studies, constant local updates are crucial to provide an adequate treatment. The propose of this study was to analyze the incidence of infectious keratitis, possible changing trends in microbiological profile, and bacteria sensitivity to commonly used antibiotics, in our tertiary center, in the last 10 years. A retrospective study was performed, based on the survey review of electronic medical records of all patients with presumed infectious keratitis, between January 1, 2009, and December 31, 2018. Microbial cultures were performed, and patients were treated according to an internal protocol. A total of 1360 samples were included. We obtained a 35.1% culture-positive rate. Bacteria accounted for 76.78% of all positive scrapes (53.34% were Gram positive and 23.44% were Gram negative), Acanthamoeba for 12.13%, fungi for 8.16%, and virus for 2.93%. The most frequent agent identified was Corynebacterium macginleyi (18.41%), followed by Staphylococcus aureus (17.78%), Streptococcus pneumoniae (9.41%), and Pseudomonas aeruginosa (9.00%). We identified at least one ophthalmologic risk factor in 410 patients (85.77%). Trauma and contact lens wear were the most common risk factors found, accounting for 34.94% (n = 167) and 33.47% (n = 160) of cases. Sensitivity to fluoroquinolones and aminoglycosides was tested in all bacterial isolates, presenting values of 96.66% and 98.12%. In our region, the most common bacteria are Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa, and they showed high sensitivity rates to first-line antibiotics, without any modification or emergence of antibiotic resistance trends during the 10 years of the study. For this reason, we decided to maintain the same internal protocol in our tertiary centre.