AIM: To indirectly compare rivaroxaban and dabigatran for prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA, TKA) based on their pivotal efficacy/safety trials embracing a total of 20618 patients. ----- METHODS: Pooled risk differences (RD) for rivaroxaban vs enoxaparin and dabigatran vs enoxaparin obtained from separate meta-analyses of two sets of trials were used to indirectly estimate RDs for rivaroxaban vs dabigatran. ----- RESULTS: Primary efficacy (any VTE+all-cause mortality) and safety (major bleeding) outcomes in enoxaparin arms largely differed across similarly designed rivaroxaban and dabigatran trials (differences in venography adjudication and bleeding events definitions). However, incidence of symptomatic VTE and incidence of major/non-major clinically relevant bleeding (including surgical site) were consistent in this respect. RDs (as percentages) for symptomatic VTE were: rivaroxaban-enoxaparin=-0.4% (95% confidence interval [CI], -0.9 to 0.05); dabigatran-enoxaparin=-0.09% (95% CI, -1.0 to 0.8); rivaroxaban-dabigatran=-0.3% (95% CI, -1.3 to 0.7; P=0.275). RDs for major/clinically relevant bleeding were rivaroxaban-enoxaparin=0.99% (95%CI, 0.29 to 1.69); dabigatran-enoxaparin=0.02% (95% CI, -1.0 to 1.0); rivaroxaban-dabigatran=0.97 (95% CI, -0.43 to 2.37; P=0.085). Mortality rates (all-cause, VTE-related, bleeding-related) were very low not indicating differences between any two of the three treatments. ----- CONCLUSION: Methodological differences disable indirect comparisons of rivaroxaban vs dabigatran that would be based on major efficacy/safety outcomes of their pivotal trials. The two drugs do not seem to differ regarding incidence of symptomatic VTE. Risk of a relevant bleeding is higher with rivaroxaban than with enoxaparin and the same tendency exists also vs dabigatran. Direct rivaroxaban vs dabigatran comparisons in this setting are needed.