Eptinezumab holds important promise in treating migraine patients, but its ideal dose is unknown. This meta-analysis aims to compare the efficacy and safety of eptinezumab 300mg versus 100mg for migraine patients. Several databases including PubMed, Web of science, EBSCO, EMbase and Cochrane library databases have been systematically searched and we included the randomized controlled trials (RCTs) assessing the effect of eptinezumab 300 mg versus 100mg for migraine patients. This meta-analysis was conducted using the random-effect model. Five RCTs and 1989 patients were included in the meta-analysis. Compared with eptinezumab 100 mg in migraine patients, eptinezumab 300 mg was associated with substantially reduced monthly migraine days (MD=-0.50; 95% CI=-0.56 to -0.44; P < 0.00001), increased 75% responder rate (OR =1.32; 95% CI =1.07 to 1.62; P = 0.008) and 50% responder rate (OR =1.24; 95% CI =1.04 to 1.48; P = 0.02), but unraveled no remarkable influence on migraine 1 day after dosing (OR =0.92; 95% CI =0.72 to 1.18; P = 0.52), adverse events (OR =1.07; 95% CI =0.81 to 1.42; P = 0.62) or serious adverse events (OR =1.60; 95% CI =0.68 to 3.74; P = 0.40). Eptinezumab 300mg was superior to eptinezumab 100mg for the treatment of migraine patients.