The aim of this study was to evaluate the efficacy of a hyaluronic acid containing eye drop in ameliorating ocular surface pathology and discomfort in canine keratoconjunctivitis sicca (KCS). Twenty five dogs with KCS treated with a topical carbomer (CA)-based tear replacement gel were moved to treatment with a hyaluronic acid (HA)-containing tear replacement eye drop. Dogs were subject to a full ophthalmic examination at the beginning of the study and after two and four weeks of treatment, Schirmer tear tests (STTs) were performed at each examination. Conjunctival hyperemia, ocular discharge and ocular irritation were evaluated and scored on a 0-3 semi-quantitative scale. Values were compared before and after 4 weeks of treatment using a paired t-test. Evaluation scores were compared using the Wilcoxon signed rank test. The transfer from CA-based to HA-containing tear replacement significantly decreased the conjunctival hyperemia score from 2.12 ± 0.73 to 1.26 ± 0.59 and ocular discomfort was lowered from 2.11 ± 0.97 to 0.93 ± 0.75. Ocular discharge was reduced from a score of 1.04 ± 0.82 to 0.70 ± 0.53, however, the decrease did not reach statistical significance. Schirmer tear test was increased with statistical significance (p < 0.001) but given that the increase was only from 5.42 ± 3.50 to 6.19 ± 3.86 mm min-1; this was not considered clinically significant. This study demonstrated that HA-containing eye drops used twice daily in dogs with KCS had greater ameliorative effects on ocular surface health and discomfort than did CA-based topical gels used as or more frequently.