Hookworm infections present a major health risk to dogs, especially in areas characterized by warmer climates and poor sanitation. This cross-sectional study was undertaken to determine the prevalence of hookworm infections and the efficacy of anthelmintic treatments in dogs from the Bono East Region of Ghana. Four hundred and ninety-one (491) canine stool samples were examined using the McMaster technique to ascertain the prevalence of hookworms. Using in vivo and in vitro techniques, the efficacy of three anthelmintics (albendazole, pyrantel, and niclosamide) was assessed in an experimental control trial involving dogs naturally infected with hookworms. The effects of the drugs on hematological and biochemical parameters were measured within a 14-day period to assess changes over time. The study found a total prevalence of 54.2% (266), with significantly higher infection rates in puppies (69.8%, 97), hunting dogs (64.1%, 91), and rural dogs (84.2%, 160). Logistic regression identified age, purpose, and settlement type as risk factors for infection. Of the three treatments, niclosamide was the most efficacious, reducing egg counts by 95%, while albendazole was the least efficacious (-69%). In vitro tests confirmed the superior performance of niclosamide, with the lowest IC