BACKGROUND: Streptococcus anginosus group is a common cause of pediatric intracranial infections but treatment recommendations, including use of oral therapy, are poorly defined. METHODS: We performed a retrospective review from 2004 to 2019 of all patients with S anginosus group pyogenic intracranial infections at Childrens Hospital Colorado, highlighting patients transitioned to oral therapy. The primary endpoint was worsening infection necessitating intravenous antibiotics or a source control procedure after transition to oral therapy. RESULTS: Of 107 patients with S anginosus intracranial infections, 61 were transitioned to exclusive oral therapy after a median intravenous duration of 37 days, overwhelmingly with a levofloxacin-based regimen. Only 1 treatment failure was noted in a patient who did not fill their prescription. Patients with epidural infections were more likely to be transitioned to oral therapy within the first 28 days of treatment (defined as early). Patients with parenchymal infections, bacteremia, co-pathogens, higher inflammatory markers, and requiring >1 source control procedure were less likely to be transitioned early to oral therapy. Complications of a central catheter and/or intravenous medications contributed to 56% of oral transitions. CONCLUSIONS: Levofloxacin-based oral regimens were effective and well tolerated. Patients with less severe infections were more likely to be transitioned early to oral therapy. Criteria for transitioning patients to oral antibiotics for intracranial infections should be established to minimize risks inherent with central catheters.