Purpose: To report three cases of fluroquinolone deposition in the cornea after topical administration post-penetrating keratoplasty. Case reports: Herein we report three patients ranging in age from 42-65 years who underwent keratoplasty with cataract extraction, with intraocular lens implantation in the first two cases and left aphakic due to a posterior capsular tear in the third case. The first two patients received ciprofloxacin-dexamethasone combination drops, and developed drug deposition, which was observed at the first follow-up after 7 and 10 days respectively. The third patient received prednisolone acetate and ofloxacin eyedrops postoperatively, and developed drug deposits in the cornea after 20 days. In all of the three patients, the fluroquinolone group of drugs was discontinued and the cornea cleared gradually over the next 3-4 weeks. Although the cornea cleared, the first two grafts failed due to recurrent viral infection in one case, and graft rejection in the other case. Conclusion: Deposition of many different fluroquinolones in the cornea has been reported after a variety of surgeries, including penetrating keratoplasty. Drug deposition post-penetrating keratoplasty may seem innocuous due to self-resolution on cessation of the drugs, but it may have deleterious effects on graft survival. Hence, fluroquinolones, especially ciprofloxacin, should be cautiously used in patients undergoing penetrating keratoplasty if frequent dosing is prescribed or if used concurrently with other topical medications containing preservatives.