Background Despite advances in diagnostic tools and therapy approaches over the last few decades, pediatric infective endocarditis (IE) remains a complicated condition. IE is associated with considerable morbidity and death. Aim of the work This research aims to revise the medical treatment of pediatric patients with IE who were admitted to the Cardiology Unit at Assiut University Children Hospital (AUCH) and how much it is adherent to the international guidelines of American Heart Association (AHA), in addition, to evaluate their outcome. Subjects and methods This clinical audit was conducted on 30 pediatric patients with IE who were admitted to the Pediatric Cardiology Unit, AUCH, Egypt from March 2020 to February 2021. In all, 76.7% of enrolled cases with IE received vancomycin 40 mg/kg per 24 h IV in 2 or 3 divided doses and 23.3% received Ceftriaxone at a dose of 100 mg/kg per dose IV or IM daily. Then the treatment was modified according to the blood culture sensitivity test for at least 4 weeks and up to 6–8 weeks in some cases. Transthoracic echocardiography (TTE) was performed for all cases at the beginning, and after finishing the treatment protocol. Evaluation for the development of complications among the studied cases was done. Results The median age of the studied participants was 7 years, 83.3% were males. According to Modified Duke Criteria, 73.3% had a definite diagnosis of IE, and 26.7% had a possible diagnosis of IE. All studied cases received immediate assessment, and general and systematic examination. The echocardiographic examination which was done revealed that 83.0% of the studied participants have no valvular lesions. After receiving the empirical treatment, all studied patients received antibiotic therapy according to the blood culture and sensitivity test results. A significant decrease in IVSD, LVESD, LVPWD diameters, and thickness, and a significant improvement in left ventricular systolic function (LVEF and LVFS) was observed in IE patients after receiving treatment. Other cardiac diameters show improvement but do not reach a significant level. Also, the vegetation size shows a significant reduction. Regarding the final outcome of the IE patients who were admitted to AUCH, 53.3% achieved recovery while 46.7% deteriorated. Conclusion The international guidelines for the management of IE-diseased children were successfully followed by the Cardiac Unit of AUCH, on average, 85.0% (as we used ceftriaxone as an empirical treatment which is not recommended by AHA), and are associated with a high success rate.