Aim of this blinded, prospective, randomized clinical study was to compare three different lubricant eye drops (LED) in healthy adult dogs undergoing general anaesthesia (GA) for non-ophthalmic surgery. Tear production rate was monitored by means of Schirmer tear test-1 (STT-1), and incidence of post-operative corneal abrasions/ulcerations was detected by corneal staining. A complete ophthalmic examination was performed before premedication, at extubation time and 24 h after GA in twenty-five non-brachycephalic dogs (fifty eyes) undergoing elective orthopaedic or spinal surgery procedures. Dogs were randomly allocated to one of three groups receiving as prophylactic LED either carmellose sodium (GC), or 1% hyaluronic acid (GH), or 0.25% hyaluronic acid (GL). In each eye STT-1 was repeated every hour during GA, before instilling one drop of the assigned LED. In all groups STT-1 values drastically decreased during GA, while 24 h later nine eyes (18%) had STT-1 values lower than 15 mm/minute. All of the three formulations tested were fully effective in preventing corneal ulceration (0% in all groups), while 10% of eyes reported superficial de-epithelialization. Fluorescein staining demonstrated that hourly prophylactic LED application prevented exposure keratopathy during general anesthesia in 90% of the eyes in non-brachycephalic dogs.