Giardia lamblia, the causative agent of giardiasis, is an intestinal infection with worldwide distribution and high rates of prevalence. Increased resistance of the parasite and the side effects of the reference drugs employed in the treatment of giardiasis make it necessary to seek new therapeutic agents. Therefore,the aim of this study was to examine the activity of hexadecylphosphocholine (miltefosine), a membrane active alkylphospholipid, that is licensed as an antileishmanial agent against giardiasis. The efficacy of miltefosine was evaluated both in vitro and in vivo in Swiss albino mice. Results of the in vitro testing revealed susceptibility of G. lamblia trophozoites to miltefosine with the following effective concentrations:EC50s of between 20 and 40 lM, and EC90s of between 20 and 80 lM. Immediate total lysis of the organisms was achieved by 100 lM. In vivo testing showed that oral administration of miltefosine,in a daily dose regimen course of 20 mg/kg for three successive days, to infected mice resulted in total elimination of the parasite from the intestine and amelioration of intestinal pathology. Scanning and transmission electron microscopy studies revealed that miltefosine induced severe morphological alterations to G. lamblia trophozoites, mainly at the level of cell membrane and adhesive disc. In conclusion,we believe that this is the first study highlighting G. lamblia as a possible new target for miltefosine.