Background: Historically, frame-based stereotactic brain biopsy (SBB) has played an important role in the diagnosis of intracranial lesions. We performed a single centre analysis of the outcomes and efficacy of SBB at the London Health Sciences Centre (LHSC). Methods: We performed a retrospective chart review of frame-based SBB from 2006 to 2017 at the LHSC. Intra-operative and final pathology reports were analyzed for biopsy diagnosis and the diagnosis was compared with pre-operative neuroimaging reports for correlation. SBB-associated morbidity and mortality were investigated using chart review and post-operative neuroimaging. Results: 173 consecutive patients were identified. The overall morbidity rate was 8.7% (15 cases) and mortality rate was 0.6% (1 case). Final biopsy diagnostic accuracy was 96%, intra-operative diagnostic accuracy was 94% and pre-operative imaging diagnostic accuracy was 65%. Elevated partial thromboplastin time and the presence of hemorrhage on post-operative CT were associated with neurological morbidity and mortality. The need to obtain three or greater samples the time of biopsy was associated with non-diagnostic biopsy. Conclusions: At the LHSC, SBB is a relatively safe and effective surgical procedure with high diagnostic yield and relatively low risk of complications. Intra-operative pathology has a high efficacy in determining diagnosis when compared to final pathology.