OBJECTIVE： To observe the clinical efficacy and safety of different combination regimens of latanoprost combined with timolol in the treatment of primary open-angle glaucoma （POAG）. METHODS： By 2×2 self-cross controlled regimen， a total of 50 POAG patients were selected from Sanya Municipal People’s Hospital during Jan. 2014-Nov. 2016， and then divided into group A and B according to random number tablet， with 25 cases in each group. Group A received traditional regimens （Latanoprost eye drops， once every night， one drop each time+Timolol maleate eye drops， once in the morning and evening， one drop each time）； after 8 weeks of treatment and 48 h washout period， group A was given modified regimen （Latanoprost eye drops， once every night， one drop each time+Timolol maleate eye drops， once every morning， one drop each time） for 8 weeks. Group B was given modified regimen； after 8 weeks of treatment and 48 h washout period， then was given traditional regimen for 8 weeks. The 24 h average intraocular pressure， peak and trough intraocular pressure before and after medication， ocular hemodynamics [end diastolic velocity（EDV）， peak systolic velocity （PSV）， resistance index （RI）]  and ADR were recorded in 2 regimens. RESULTS： After received two regimens， 24 h average intraocular pressure， peak and trough intraocular pressure， intraocular pressure fluctuation and RI were significantly lower than before treatment， while EDV and PSV were significantly higher than before treatment， with statistical significance （P＜0.05）. There was no statistical significance between 2 groups （P＞0.05）. The total incidence of ADR in patients receiving modified regimen was significantly lower than those receiving traditional regimen （4.0％ vs. 22.0％）， with statistical significance （P＜0.05）. CONCLUSIONS： In traditional combination regimen of latanoprost combined with timolol， the frequency of timolol use was changed from twice in the morning and evening to once in the morning， which doesn’t influence therapeutic efficacy but reduce ADR.