Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteraemia in neutropenic patients. In this retrospective single centre cohort study, we investigated the prevalence of ceftriaxone resistance in VS (CRO-R VS) blood isolates between January 2005 and December 2022 from patients treated at a tertiary care hospital. Blood culture isolates were identified using biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby-Bauer and Epsilometer tests. Demographic data, clinical outcomes and antimicrobial use were assessed through electronic medical record review. Among 791 patients with VS bacteraemia, 31 (4%) had confirmed CRO-R VS bacteraemia over the 18-year period; 20/31 (65%) were patients also treated at the Fred Hutchinson Cancer Center and were the focus of this study. Of these 20 patients, 18 (90%) had a known haematologic malignancy; 14 (70%) had undergone haematopoietic cell transplant (HCT); 18 (90%) were neutropenic at the time of culture. Two (10%) patients died within 30 days of CRO-R VS bacteraemia. All the CRO-R isolates (20/20) were members of the Streptococcus mitis group, 12 were multi-drug resistant; all were susceptible to vancomycin. Most patients received vancomycin once blood cultures were positive for a Gram-positive organism. During the study period, the frequency of VS isolate susceptibility testing increased; however, there was no concomitant increase in the percentage of CRO-R isolates at our facility. These data are important in an era where cefepime monotherapy is often used and reinforces the importance of routine resistance testing among VS bacteraemia.