BACKGROUND: Stereoelectroencephalography (SEEG) is an established diagnostic technique for the localization of the epileptogenic zone in drug-resistant epilepsy. In vivo accuracy of SEEG electrode positioning is of paramount importance since higher accuracy may lead to more precise resective surgery, better seizure outcome and reduction of complications. OBJECTIVE: To describe experiences with the SEEG technique in our comprehensive epilepsy center, to illustrate surgical methodology, to evaluate in vivo application accuracy and to consider the diagnostic yield of SEEG implantations. METHODS: All patients who underwent SEEG implantations between September 2008 and April 2016 were analyzed. Planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative imaging. Quantitative analysis of deviation using Euclidean distance and directional errors was performed. Explanatory variables for electrode accuracy were analyzed using linear regression modeling. The surgical methodology, procedure-related complications and diagnostic yield were reported. RESULTS: Seventy-six implantations were performed in 71 patients, and a total of 902 electrodes were implanted. Median entry and target point deviations were 1.54 mm and 2.93 mm. Several factors that predicted entry and target point accuracy were identified. The rate of major complications was 2.6%. SEEG led to surgical therapy of various modalities in 53 patients (69.7%). CONCLUSIONS: This study demonstrated that entry and target point localization errors can be predicted by linear regression models, which can aid in identification of high-risk electrode trajectories and further enhancement of accuracy. SEEG is a reliable technique, as demonstrated by the high accuracy of conventional frame-based implantation methodology and the good diagnostic yield.