We sought to establish a benchmark for complications using frame-based stereotactic surgery for both deep and lobar brain surgery. During a 28-year interval, we performed frame-based stereotactic surgery in 2,651 patients. Our database was retrospectively used to assess the risks of complications after frame-based stereotactic surgery.Routine immediate intraoperative imaging detected new blood products after diagnostic biopsy in 43 cases (2.6%); only 6 patients (0.36%) required craniotomy for hematoma evacuation. Perioperative seizures occurred in 6 patients (0.36%), and 2 patients developed burr hole site infections. One patient (1%) developed an intra-abscess hemorrhage after biopsy and catheter drainage. Two deaths (0.08%) related to surgery occurred. Some centers are currently migrating to frameless, even pinless, neuronavigation-guided needle procedures for both lobar and deep brain targets. Although experimental accuracy under optimal conditions is reported to be similar to that of frame-based systems, the complication rates from a significant number of cases have yet to be reported. This report establishes the safety profile of frame-based stereotactic surgery based on a 28-year period. These results may serve as a benchmark against which free-hand or guided neuronavigation approaches may be measured, as both the advantages and risks of such procedures are assessed.