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Purpose To evaluate the safety and efficacy of the timolol/dorzolamide fixed combination vs latanoprost 0.005% in exfoliation glaucoma patients. Methods We randomized in an observermasked fashion 65 newly diagnosed exfoliation glaucoma patients to either the timolol/dorzolamide twice daily or latanoprost daily treatment for 2 months and then crossed these over to the other treatment. Results A total of fifty-four patients completed the study. After 2 months of chronic dosing, the morning intraocular pressure (IOP) (10:00) was reduced from a baseline of 31.276.5 mmHg to 18.173.0 with the fixed combination and to 18.974.1 mmHg with latanoprost (P ¼ 0.21). Six patients were discontinued early from both treatment periods owing to inadequate IOP control and two others were discontinued from latanoprost treatment only. The fixed combination showed a significantly greater incidence of taste perversion (Po0.001) and stinging upon instillation (P ¼ 0.036), while latanoprost showed a trend for increased conjunctival injection (P ¼ 0.056). However, five patients demonstrated either bradycardia or asthmatic symptoms with initiation of the fixed combination therapy. One patient on latanoprost complained of dizziness. Patient preference was generally given to latanoprost (63 vs 20.3%) mainly because of its once daily dosing (Po0001). Conclusions This study suggests that both latanoprost and the timolol/dorzolamide fixed combination are efficacious in the treatment of newly diagnosed exfoliation glaucoma.