Development of cataracts is a relatively frequent ocular disease of the dog and cataract extraction via phacoemulsification (PE) is commonly performed by veterinary ophthalmologists. Postoperative ocular hypertension (POH) describes the elevation of pressures within the eye during the acute postoperative period and can result in vision loss and poor surgical outcome. Relatively little is known about risk factors or efficacy of prophylactic treatment for POH, and current clinical practice with regard to pressure monitoring and medication administration are highly variable. The literature on POH prophylaxis in humans indicates that improved efficacy may be achieved with a multi-dose approach and that dorzolamide hydrochloride/timolol maleate (DHTM) may be more efficacious than other pressure lowering medications. The canine literature on POH prophylaxis is limited and DHTM has not yet been evaluated despite common use in the clinical setting. Our objectives, therefore, were to investigate risk factors for POH and to test the hypothesis that perioperative topical ophthalmic dorzolamide hydrochloride 2%/timolol maleate 0.5% (DHTM) reduces the prevalence and/or severity of postoperative ocular hypertension (POH) in dogs undergoing cataract extraction by phacoemulsification (PE). We employed a randomized double-masked placebo-controlled study and enrolled 103 dogs (180 eyes) presenting for unilateral or bilateral PE. Select historical, signalment, ophthalmic examination, and surgical data was collected. Dogs were treated with DHTM or Blink Contacts (BC) placebo at 14and 2-h preoperatively and at conclusion of surgical closure. Intraocular pressures were assessed by rebound tonometry at 2, 4, 6, and 8 hours after surgery and at 8 am the following morning. POH was defined as IOP>25 mmHg and intervention consisted of latanoprost 0.005% if IOP rose to 26 mmHg 45 mmHg or surgeon treatment of choice if >45 mmHg. Our investigation of risk factors yielded a statistically significant association only with surgeon and surgical time, which were also associated with one another. DHTM significantly reduced the prevalence of POH in comparison with BC (26% versus 49% of eyes, OR=0.36; 34% versus 62% of dogs, OR=0.32). There was also a trend toward reduction of POH severity in DHTM-treated eyes (POH value 37.17±10.47 mmHg with BC, 32.67±6.39 mmHg with DHTM). DHTM-treated eyes that developed POH were significantly more likely to respond favorably (1 hour post-treatment IOP <25 mmHg) to treatment with latanoprost than those in the BC group (76% versus 51%, OR=3.87). We conclude that multi-dose perioperative administration of DHTM may be recommended in dogs undergoing PE to reduce the risk of POH and improve responsiveness of POH to treatment with latanoprost.