What is known and objective? Since comprehensive medication has an important role in the initial management of patients presenting with acute primary angle closure, it is necessary to analyse the effect of each drug on alleviating the disease. This study aimed to evaluate the intraocular pressure-lowering effect of brinzolamide in the sequential treatment of acute primary angle closure. Methods In this randomized double-blind controlled trial, a total of 131 eyes of 125 consecutive patients who presented with their first episode of acute primary angle closure were recruited and received sequential treatment. In this treatment, in the absence of remission, anti-glaucoma drugs, anterior chamber paracentesis and argon laser peripheral iridoplasty are used sequentially. The patients were randomized to receive either brinzolamide or normal saline as a placebo. The primary outcomes were decreased intraocular pressure, success rate and treatment time. Results and discussion There was no statistically significant difference in the decreased level of intraocular pressure between the two groups at 6, 12 or 24 h after the start of treatment (p-values were 0.526, 0.206 and 0.130 respectively). The success rate and treatment time were also not significantly different between the groups. No adverse side effects of brinzolamide were observed in the brinzolamide group. What is new and conclusion? In patients with a first episode of acute primary angle closure, brinzolamide did not improve the effectiveness of the sequential treatment for reducing the intraocular pressure levels or shortening the treatment time within the first 24 h of initiating therapy.