Abstract Purpose The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate the effect of adding nimodipine to the guiding catheter flush (GCF) to prevent vasospasm during EVT. Methods This is a single-center retrospective analysis including patients with EVT (stent-retriever and/or distal aspiration) treated for anterior or posterior circulation intracranial vessel occlusion from January 2018 to June 2023. Exclusion criteria were intracranial or extracranial stenosis, intra-arterial alteplase, patient age over 80 years. Study groups were patients with (nimo+) and without (nimo−) nimodipine in the GCF. They were compared for occurrence of vasospasm as primary endpoint and clinical outcome in univariate analysis. Results 477 patients were included in the analysis (nimo+ n = 94 vs. nimo− n = 383). Nimo+ patients experienced less vasospasm during EVT (e.g. vasospasm in target vessel n (%): nimo− = 113 (29.6) vs. nimo+ = 9 (9.6), p < 0.001; extracranial vasospasm, n (%): nimo− = 68 (17.8) vs. nimo+ = 7 (7.4), p = 0.017). Patients of the two study groups had a comparable clinical outcome (90 day mRS, median (IQR): 3 (1–6) for both groups, p = 0.896). In general, patients with anterior circulation target vessel occlusion (TVO) experienced more vasospasm (anterior circ. TVO 38.7% vs. posterior circ. 7.5%, p = 0.006). Conclusion Prophylactic adding of nimodipine reduces the risk of vasospasm during EVT without affecting the clinical outcome. Patients with anterior circulation TVO experienced more vasospasm compared to posterior circulation TVO.