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The purpose of this article was to study the intraocular pressure (IOP)-lowering effect of adding brimonidine as the fourth antiglaucoma medication to a preexisting therapy of 3 topical drugs.This was a retrospective, register-based, cohort study of medical records and computerized medical information comprising 1 county in Sweden. The main outcome measure was change in IOP after brimonidine addition. Short-term and long-term effects were evaluated.Of 4910 patients on antiglaucoma medication, 69 (1.4%) initiated a treatment with brimonidine as the fourth drug during 2014. Fifty-three patients were eligible for analysis. Forty-six patients tolerated the treatment. Among them, short-term IOP decreased by 17% (confidence interval, 10%-25%; P<0.001) after a mean of 46 days (SD, 50 d). Twenty-eight patients, that is, 53% of the eligible, remained on unchanged therapy after a mean follow-up time of 368 days (SD, 61 d). The long-term mean IOP decrease in this group was 20% (confidence interval, 11%-29%; P<0.0001). An IOP reduction of at least 20% was reached by 28 and 14 patients, in the short-term and long-term follow-ups, respectively.Brimonidine has the potential to reduce the IOP significantly even when used as the fourth drug. In the short-term, half of the patients reached the target IOP reduction (≥20%). After 1 year, a quarter of the eligible patients had had a sustained, uneventful effect. Thus, brimonidine as the fourth adjunctive antiglaucoma drop seems a valuable option for a minority of patients.