Background: Enterobius vermicularis is one of the most common parasitic helminths causing infection in children worldwide causing distressing lifestyle and health problems. The empirical use of anthelminthic drugs without medical supervision and low compliance to treatment protocols lead to resistance to therapy. Objective: To assess the efficacy of albendazole mass treatment alone compared to the combined albendazole-flubendazole regimen for treatment of recurrent and resistant Enterobius vermicularis infection in children and their families. Subject and Methods: It was a clinical trial that included 130 children 3-12 years old with resistant Enterobius vermicularis infection determined by the following inclusion criteria for treatment resistance. This study was carried out at the Pediatrics outpatient Clinic at Al-Azhar University Hospitals, and the Medical Parasitology Department at Damietta Faculty of Medicine, Al-Azhar University at New Damietta city, Egypt. Results: 36 out of 65 (55.4%) children in the albendazole treated group and 54 out of 65(83.1%) in the albendazole-flubendazole treated group was cured with significantly higher efficacy for the albendazole-flubendazole regimen. The laboratory data showed improvement in post-treatment phase especially for albendazole- flubendazole treated groups for hemoglobin%, total leukocytic counts, neutrophil and lymphocyte counts that improved by time and a decline in the reported eosinophilia. The clinical data were significantly warning the presence of infection however they did not define the significance of treatment efficacy or resistance. Conclusion: Enterobiasis is a childhood health problem with potential resistance to regular therapeutic protocols. Using albendazole- flubendazole combined regimen showed promising results in the treated groups superior to albendazole alone against resistant Enterobius vermicularis infection in children. This gives promising results encouraging further evaluation studies.