OBJECTIVE To evaluate 24-hour intraocular pressure (IOP) efficacy of latanoprost versus travoprost, each given every evening, in exfoliative glaucoma patients. DESIGN Prospective, observer-masked, crossover comparison. PARTICIPANTS Forty patients with exfoliation glaucoma. METHODS Patients with a pressure of >24 mmHg were randomized to latanoprost or travoprost for an 8-week treatment period after a 6-week medicine-free period. Patients were then switched to the opposite treatment for the second period. At untreated baseline and at the end of each treatment period the IOP was measured at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2 am. MAIN OUTCOME MEASURE Diurnal IOP. RESULTS The mean 24-hour IOP was 25.1+/-2.5 mmHg at baseline, 17.8+/-2.1 mmHg on latanoprost, and 17.3+/-2.2 mmHg on travoprost (P = 0.001). Individual time points were similar between treatments, except at 6 pm when travoprost provided lower IOP (16.7+/-2.6 vs 17.9+/-2.5 mmHg, P<0.001). Adverse events showed more conjunctival hyperemia with travoprost (n = 15) than latanoprost (n = 6; P = 0.03). CONCLUSIONS Latanoprost and travoprost both significantly reduce the 24-hour IOP from baseline in exfoliative glaucoma, but travoprost may demonstrate a greater hypotensive efficacy in the late afternoon.