Viridans group streptococci (VGS) are an important cause of sepsis in children with cancer. Penicillin-resistance amongst VGS isolates is increasing. At our institution, vancomycin is added to standard empiric therapy for febrile neutropaenia in patients at high-risk of VGS sepsis. We reviewed effectiveness of this risk-stratified approach by examining episodes of VGS bacteraemia over three years. In 19 VGS bloodstream infection episodes, 100% of isolates from high-risk patients and 78.9% of all episodes were susceptible to risk-stratified empiric antibiotics. Based on blood culture time-to-positivity, empiric vancomycin can be safely discontinued in stable patients with no growth at 24 hours.