Abstract Background The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures. Methods All elective surgeries performed at our neurosurgical department between 01/2018–08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018–04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020–08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk. Results VTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group. Conclusion The use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.