The Aim of this study was to compare the clinical efficacy and safety of non-fixed combination (NFC) of dorzolamide (2.0%)/timolol maleate (0.5%) versus NFC of latanoprost (0.005%)/timolol maleate (0.5%) regarding reduction of intra ocular pressure in patients with primary open angle glaucoma. This was a 12-week, randomized, open label, parallel group study with primary open angle glaucoma (IOP range: 24 – 36 mmhg), which included 40 subjects in dorzolamide/timolol group [dorzolamide (2.0%) instilled twice daily and timolol maleate (0.5%) twice daily] and 40 subjects in latanoprost/timolol group [latanoprost (0.005%) instilled once daily, timolol maleate (0.5%) twice daily]. IOP was measured at baseline, 4 and 12 weeks at 10 am. Adverse events were recorded at each visit. The difference in reduction of IOP in two treatment groups from baseline to 12 weeks was the main outcome measure. Mean IOP was similar at baseline for both groups. Absolute reduction in IOP from baseline to 12 weeks was 9.6 mmhg in dorzolamide/timolol group (P <0.001) and 9.7 mmhg in latanoprost/timolol group (P <0.001). No significant difference was found regarding reduction of IOP between the groups (P < 0.85). Both treatments were well tolerated. NFC of dorzolamide/timolol and latanoprost/timolol showed comparable efficacy in reducing IOP. They were also comparable regarding safety profile.