OBJECTIVES: Non-compliance is frequently reported as a cause of treatment failure of oral antimicrobials. As the long-term injectable cefovecin eliminates non-compliance, the study objective was to investigate the impact of non-compliance on the costs and effectiveness of treatment of superficial pyoderma, wounds and abscesses (SP-W-A), and deep pyoderma (DP) in dogs in Germany. METHODS: A Markov model, containing the health states “Worsening”, “Status quo”, “Improvement”, “Cure”, and “Relapse”, was adapted to Germany to calculate costs and benefits (days without symptoms of SP-W-A or DP) over a 6-months (SP-WA) and 1-year (DP) period, for dogs on cefovecin versus amoxicillin/clavulanic acid (amoxi/clav). Efficacy parameters were derived from clinical studies. For amoxi/clav, first line treatment failure caused by non-compliance was estimated at 13.6% of all dogs, calculated from published literature. Cost data were derived from German official price and tariff lists (2009, dog owner’s perspective). All relevant input parameters were varied extensively in one-way and probabilistic sensitivity analyses. RESULTS: Cefovecin was more effective than amoxi/clav, with 161 versus 156 days without symptoms of SP-W-A and 316 versus 307 days without symptoms of DP. Up to a bodyweight (b.w.) of 15 kg (SP-W-A) or 16 kg (DP), cefovecin was a dominant strategy, i.e. also cost-saving when considering total therapy expenditure (including anamnesis, diagnosis, treatment). In dogs of 25 kg b.w., total therapy costs for cefovecin were slightly increased versus comparator, €297.25 versus €272.72 (SP-W-A) and € 498.60 versus €477.75 (DP). Model outcomes were sensitive to changes of non-compliance data, but remained robust when varying other parameters. CONCLUSIONS: Considering non-compliance with oral treatments as a cause of treatment failure, higher drug and administration costs of cefovecin became totally or partly offset by the increased incremental efficacy resulting in less costs for supplementary treatments of relapses and failures.