OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has considerably affected surgical practice. The present study aimed to investigate the effects of the pandemic on neurosurgical practice and the safety of the resumption of elective procedures through implementing screening protocols in a high-volume academic public center in Iran, as one of the countries severely affected by the pandemic. METHODS: This unmatched case-control study compared 2 populations of patients who underwent neurosurgical procedures between June 1, 2019 and September 1, 2019 and the same period in 2020. In the prospective part of the study, patients who underwent elective procedures were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection postoperatively to evaluate the viability of our screening protocol. RESULTS: Elective and emergency procedures showed significant reduction during the pandemic (59.4%, n = 168 vs. 71.3%, n = 380) and increase (28.7%, n = 153 vs. 40.6%, n = 115, respectively; P = 0.003). The proportional distribution of neurosurgical categories remained unchanged during the pandemic. Poisson regression showed that the reduction in total daily admissions and some categories, including spine, trauma, oncology, and infection were significantly correlated with the pandemic. Among patients who underwent elective procedures, 0 (0.0%) and 26 (16.25%) had positive test results on days 30 and 60 postoperatively, respectively. Overall mortality was comparable between the pre-COVID-19 and COVID-19 periods, yet patients with concurrent SARS-CoV-2 infection showed substantially higher mortality (65%). CONCLUSIONS: By implementing safety and screening protocols with proper resource allocation, the emergency care capacity can be maintained and the risk minimized of hospital-acquired SARS-CoV-2 infection, complications, and mortality among neurosurgical patients during the pandemic. Similarly, for elective procedures, according to available resources, hospital beds can be allocated for patients with a higher risk of delayed hospitalization and those who are concerned about the risk of hospital-acquired infection can be reassured.