Ceftriaxone-induced neutropenia is a rare and severe adverse effect of the drug. It usually resolves in one to three weeks following the cessation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). After neutrophil recovery, patients are often treated with non-β-lactam antibiotics instead of ceftriaxone due to the possibility of cross-reactivity associated with β-lactam allergy. However, in some cases, β-lactam antibiotics are superior to non-β-lactam antibiotics. Few cases of the readministration of β-lactam antibiotics for patients who developed ceftriaxone-induced neutropenia have been reported so far. Moreover, its pathogenesis and management have still not been established. We describe a case of successful readministration of β-lactam antibiotics for a patient who had developed ceftriaxone-induced neutropenia. A 37-year-old man with a prosthetic aortic valve was admitted to our hospital with a fever. Blood culture on admission revealed methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, and transesophageal echocardiography (TEE) showed aortic valve vegetation with multiple septic emboli seen on brain CT. We diagnosed MSSA infective endocarditis with central nervous complications. He underwent an operation and was treated with ceftriaxone. On admission day 28, he developed neutropenia (33/μL), and ceftriaxone-induced neutropenia was suspected. Vancomycin was started instead of ceftriaxone, and his neutrophil count recovered within two weeks with the administration of G-CSF. After recovery, on day 40 of admission, ampicillin sodium was administered instead of vancomycin. Although he developed mild eosinophilia, he did not exhibit neutropenia and was discharged with an amoxicillin prescription on day 60 of admission.Our report suggests the possibility that patients who develop ceftriaxone-induced neutropenia can be treated safely with an alternative β-lactam antibiotic, ampicillin sodium, without causing β-lactam cross-reactivity of neutropenia.