Purpose: To assess the effects of topical latanoprost 0.005% versus brimonidine tartrate 0.2% on perfusion of optic nerve head in patients with POAG using optical coherence tomography angiography. Patients and methods: This study included 56 patients with bilateral POAG divided into two groups, 28 patients in each (nine patients, five in group I and four in group II were excluded). Group I included 23 patients (46 eyes) treated with latanoprost 0.005% eye drops, while 24 patients (48 eyes) received treatment with brimonidine tartrate 0.2% eye drops in group II. All patients underwent radial peripapillary capillary vessel density (VD) measurement using optical coherence tomography angiography, intra ocular pressure (IOP) measurement and mean ocular perfusion pressure (MOPP) calculation before starting treatment, one and three months after treatment. Results: A total of 12 males were included in group I while group II included 14 males. The mean presenting initial IOP was 27.4±1.9 mmHg and 26.3±1.8 mmHg that decreased after 3 months, at the end of follow-up, to 13.8±0.8 mmHg and 13.5 ±0.7 in group I and group II, respectively, which was statistically significant (P<0.005), with no significant difference in post treatment IOP between both groups. The whole VD was improved from 35.3±1.2% and 32.1±1.1 before treatment to 47.6±0.9% and 40.8±0.6% 3 months after treatment in group I and group II, respectively, with percentage increase 34.8% and 27.1% that was statistically significant. The difference in percentage change between both groups was also significant (P<0.005) with superior improvement in group I. The VD increased significantly in all quadrants compared with the initial VD in both groups, with superior improvement in group I in comparison to group II (P<0.005). The mean ocular perfusion pressure was significantly improved in both groups after treatment in both groups. Conclusion: Both latanoprost and brimonidine eye drops improved the optic head perfusion innPOAG with superior effect of latanoprost.