The aim of this study was to comparatively evaluate the efficacy of different antimicrobial agents against interdigital necrobacillosis (IN) in cattle to identify the treatment with the greatest benefit. A network meta-analysis was used to synthesise empirical results from randomised controlled trials. Four studies with five interventions for 565 animals were included. The meta-analysis found no significant differences between the risk ratios for the antimicrobials versus placebo. However, ceftiofur sodium administered intramuscularly at a dose of 1.0 µg/kg body weight every 24 h for 3 days showed a better clinical response than 6.6 µg of oxytetracycline, 2.5 µg of tulathromycin, the placebo and 0.1 µg of ceftiofur sodium. The results show the best efficacy for 6.6 µg of oxytetracycline and 1.0 µg of ceftiofur sodium. Nevertheless, the latter is likely to be superior to oxytetracycline in terms of its pharmacodynamic and pharmacokinetic properties. Thus, 1.0 µg of ceftiofur sodium appears to provide the best therapeutic activity against IN in cattle. Further well-designed studies are required.