AIM: To compare the safety and efficacy of subconjunctival injection with conbercept and 5-fluorouracil (5-FU) for open angle glaucoma (OAG) patients after filtration surgery. METHODS: As a prospective randomized interventional trial, 36 eyes from 36 patients after OAG surgery were collected and divided randomly into conbercept and 5-FU groups. All patients were subconjunctivally injected with either conbercept (0.2 mL) or 5-FU (0.2 mL) on the 5th day post-operatively. The intraocular pressure (IOP), number of medications used, type of conjunctival bleb, and complications were recorded and analyzed pre-operatively and 1d, 1wk, 1, 3 and 6mo post-injection. RESULTS: There were significant differences in IOP between the conbercept and 5-FU groups 1mo (conbercept group: 12.17±1.04 mm Hg; 5-FU group: 13.50±2.33 mm Hg, t=2.214, P=0.037), 3mo (conbercept group: 13.00±1.88 mm Hg; 5-FU group: 14.50±2.28 mm Hg, t=2.153, P=0.039), and 6mo post-injection (conbercept group: 13.28±2.95 mm Hg; 5-FU group: 15.22±2.49 mm Hg, t=2.140, P=0.040); however, in the number of medications, a prominent difference was not shown between groups on post-injection 6mo (t=1.312, P=0.200). Moreover, there was mild vascularity observed in the conbecept group than the 5-FU group 1d (3a, 3b, 3c: t=8.497, 6.693, 4.515, P=0.000), 1wk (3a, 3b, 3c: t=3.431, 6.408, 3.984, P=0.002, 0.000, 0.000), and 1mo post-injection (3a, 3b, 3c: t=2.466, 2.466, 2.503, P=0.019, 0.019, 0.017). Simultaneously, differences from other indicators between the two groups were not demonstrated. Also, there was a lower probability of corneal epithelial stripping in the conbercept group than the 5-FU group (χ2=4.500, P=0.034). CONCLUSION: Subconjunctival injection of conbercept has a safe, effective, and tolerable profile for open angle glaucoma patients with distinct conjunctival congestion after filtration surgery.