•Clinical efficiency of artesunate in resistant CMV infections is controversial.•We describe 5 cases of multidrug-resistant CMV infections treated with artesunate.•Clinical outcomes was favourable in 3 cases and unfavourable in 2 cases.•Artesunate was useful in decreasing CMV DNA load in multidrug-resistant CMV strains.•Artesunate was insufficient for the treatment of severe illness with organ injury. Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.