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Minor bleeding is the most common complication of dermatologic surgery. Topical brimonidine, 0.33%, gel has been reported for the use of hemostasis in dermatologic surgery. The safety profile and risk of systemic toxic effects when brimonidine is used topically for hemostasis is unknown.To determine the risk of systemic toxic effects of topical brimonidine, 0.33%, gel when used for hemostasis.In this case series from a private practice (Hollywood Dermatology), 2 patients presented for dermatologic procedures, complicated by persistent bleeding.Patients were treated with 10 g of brimonidine, 0.33%, gel applied under occlusion for hemostasis.Mental status, cardiopulmonary function.Both patients experienced deterioration of mental status, respiratory depression, and somnolence. Results from cardiac testing, laboratory workup, and imaging were negative for cardiac or neurologic etiology. Both patients improved in less than 24 hours.Topical brimonidine, 0.33%, gel can result in systemic central nervous system toxic effects when used as a hemostatic agent. At present, it is not possible to define a quantity with which brimonidine can be used safely, nor can a safe wound size be defined. We, therefore, urge against the use of topical brimonidine as a hemostatic agent until its safety is further investigated.