The control of extracellular nucleoside concentrations by Nu-cleoside Triphosphate Diphosphohydrolase (NTPDase) is essential in the regulation of the purinergic signalling and also in immune response. In humans, eight members (HsNTPDase) were identified as transmembrane and secreted proteins. In Schistosoma mansoni, the causative agent of schistosomiasis, NTPDases similar to the humans enzymes have also been identified. The expression of these enzymes in S. mansoni (SmATPDases) is related to the weakening of the immune and inflammatory responses of the host against infections. Despite of the high phylogenetic conserva-tion between these proteins, SmATPDases have been reported as molec-ular target candidates for antischistosomal treatment. In this work, we constructed three-dimensional models for secreted SmATPDase and HsNTPDase6, using comparative modeling technique. The comparative structural analysis aim the investigation of possible differences that could help future works in the development of new therapies that minimize the risk of cross inhibition.