Aim and Background: Fascioliasis is the most important parasitic diseases that affect the human and animal all over the world. Triclabendazole (TCBZ), and Mirazid is the most common trematodicidal drug used in Egypt The present study, aimed to evaluate the therapeutic efficacy of the TCBZ and Mirazid in Guinea pigs experimentally infected with Fasciola gigantica Methods: Thirty two, Guinea pig (1-2 month old) was allocated into four equal groups to study the efficacy of treatment of facioliasis with triclabendazole (TCBZ) and mirazid. Group (Gp.1) was the control, GPs (2 -4) were orally inoculated with 20 Fasciola giganticametacercariae (FGM) for each as a single dose by using stomach tube. Gps (3&4) were treated orally, with TCBZ, as a single dose (36 mg/Kg Bw) and mirazid 200 mg/ Kg Bw for six successive days respectively. The drugs were administered in the 8th week post-infection to evaluate their efficacy against adult stages of Fasciola gigantica. Blood samples were collected at the end of the 1st and 2nd week post treatment for hematological and serum biochemical examination. Results:TCBZ treated groups (GP 3) showed macrocytic hypochromic anemia, which disappeared at the end of the 2nd week post treatment. Heterophilia, esinophilia and lymphopenia were encountered in non treated group (GP 2) and mirazid treated group (GP 4). The liver transaminase (ALT, AST), gamma glytamyl transferase (GGT) and alkaline phosphatase (ALP) as well as total bilirubin, urea and creatinine, were elevated while serum albumin was decreased in GP (2) and returned to the normal value in GP (3) and GP (4) after two weeks post-treatment. Conclusion:It could be concluded that; the triclabendazole is more effective than mirazid in the treatment of Fasciola giganticainfection. Further research should be done for more precise knowledge about the efficacy of mirazid as a fasciolicidal drug.