Coxsackievirus B3 (CVB3) represents a major etiological factor of viral myocarditis (VMC). It frequently results in the damage of the heart and even heart failure, but there are few effective treatment measures that can be used clinically. In this paper, we show that abietic acid (AA), a tricyclic diterpenoid compound, has strong anti-CVB3 activity both in vitro and in vivo. AA was found to inhibit CVB3 replication with 50% effective concentration (EC50) of 12.16 μM and high selectivity index (S