Coronavirus disease 2019 (Covid-19) is associated with a hypercoagulable state. It has been hypothesized that higher-dose anticoagulation, including therapeutic-dose and intermediate-dose anticoagulation, is superior to prophylactic-dose anticoagulation in the treatment of Covid-19. This meta-analysis evaluated the efficacy and safety of higher-dose anticoagulation compared with prophylactic-dose anticoagulation in patients with Covid-19. Ten randomized controlled open-label trials with a total of 5,753 patients were included. The risk of death and net adverse clinical events (including death, thromboembolic events, and major bleeding) were similar between higher-dose and prophylactic-dose anticoagulation (risk ratio (RR) 0.96, 95%CI, 0.79-1.16, P=0.66 and RR 0.87, 95%CI, 0.73-1.03, P=0.11, respectively). Higher-dose anticoagulation, compared with prophylactic-dose anticoagulation, decreased the risk of thromboembolic events (RR 0.63, 95%CI, 0.47-0.84, P=0.002) but increased the risk of major bleeding (RR 1.76, 95%CI, 1.19-2.62, P=0.005). The risk of death showed no statistically significant difference between higher-dose anticoagulation and prophylactic-dose anticoagulation in non-critically ill patients (RR 0.87, 95%CI, 0.50-1.52, P=0.62) and in critically ill patients with Covid-19 (RR 1.04, 95%CI, 0.93-1.17, P=0.5). The risk of death was similar between therapeutic-dose versus prophylactic-dose anticoagulation (RR 0.92, 95%CI 0.69-1.21, P=0.54) and between intermediate-dose versus prophylactic-dose anticoagulation (RR 1.01, 95%CI 0.63-1.61, P=0.98). In patients with markedly increased d-dimer levels, higher-dose anticoagulation was also not associated with a decreased risk of death as compared with prophylactic-dose anticoagulation (RR 0.86, 95%CI, 0.64-1.16, P=0.34). Without any clear evidence of survival benefit, these findings do not support the routine use of therapeutic-dose or intermediate-dose anticoagulation in critically or non-critically ill patients with Covid-19.