The therapeutic efficacy of different doses of albendazole (ABZ) in the treatment of infection by acanthocephalan (Neoechinorhynchus buttnerae) in tambaqui (Colossoma macropomum) was evaluated. The bioaccumulation of ABZ and its main metabolites in the target tissue (muscle plus skin in natural proportions) was also evaluated. The fish received a daily dose of 10, 20 or 30 mg ABZ kg −1 bw via medicated feed for 34 days.Incorporation of ABZ in the fish feed was performed by coating with ethyl cellulose (EC) (0.75% w/w). The quantitation of ABZ residues and its metabolites in the target tissue was done using a validated ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS/MS) analytical method. In relation with the therapeutic efficacy, no statistically difference was found between the treated groups. The total residue (sum of ABZ residues and its metabolites) in the target tissue at steady-state was significantly higher for the high dose. Biomagnification factors in all treatments were of low values, indicating that ABZ and its metabolites do not offer the risk of bioaccumulation in the target tissue. Thus, ABZ dose of 10 mg kg −1 bw is recommend. However, the effect of feed coating on treatment effectiveness and bioaccumulation of albendazole relative to an uncoated feed, and joint therapeutic studies of ABZ with anthelmintic natural products are recommended to be conducted.