To evaluate the 24-hour intraocular pressure (IOP)–lowering effect of latanoprost and the dorzolamide/timolol fixed combination (DTFC) after 2 and 6 months of treatment.Randomized, prospective, crossover comparison.Thirty-nine patients had primary open-angle glaucoma, and 14 patients had ocular hypertension.After a 6-week washout period, patients were randomized to either 6 months of treatment with the DTFC twice daily or latanoprost every evening and then crossed over to the opposite treatment for an additional 6 months.Mean 24-hour IOP after 2 and 6 months of treatment.Fifty-three patients had an average 24-hour baseline IOP of 25.2±2.3 mmHg. After 6 months of treatment, 24-hour IOPs were 18.1±1.9 mmHg for the DTFC and 18.3±1.9 mmHg for latanoprost. Compared with 2 months of therapy, at 6 months the DTFC showed no significant change in mean 24-hour IOP, whereas latanoprost demonstrated a reduction of 0.3 mmHg (P = 0.01). The DTFC had more burning (P<0.001) and bitter taste (P = 0.01), whereas the latanoprost had more hypertrichosis (P = 0.02).After 6 months of therapy, the DTFC and latanoprost have clinically similar 24-hour IOP-lowering efficacies.