Root rot disease caused by Pythium myriotylum is a major threat to cocoyam cultivation in Cameroon. Control methods based on agricultural practices and chemical treatments have limitations. Since biocontrol is an interesting alternative, this study assessed the potential of four Trichoderma asperellum strains to control P. myriotylum. The antagonistic and mycoparasitic potential of the T. asperellum strains was evaluated in vitro through dual culture and interaction tests. Subsequently, the ability of T. asperellum to protect cocoyam plants from P. myriotylum infectionwas tested in vivo. Our results showed that all four T. asperellum strains were antagonistic to P. myriotylum, although differences were found among the strains. The growth of P. myriotylum was inhibited by more than 60%. Furthermore, the four T. asperellum strains were aggressive mycoparasites of P. myriotylum. In in vivo trials, pretreatment of cocoyam plants with the strains PR10 and PR11 of T. asperellum could reduce P. myriotylum infection by 50%. Both PR10 and PR11 strains of T. asperellum present promising biocontrol potential against P. myriotylum.