Background and purpose: Vasospasm is a common complication of endovascular therapy (EVT). There is a lack of understanding of risk factors for periprocedural vasospasm. Here, we aimed to identify factors associated with vasospasm in patients with acute ischemic stroke who undergo EVT. Methods: We conducted a retrospective single-center analysis of patients receiving EVT for anterior circulation vessel occlusion between January 2015 and December 2021. Patients were excluded if they showed signs of intracranial atherosclerotic disease (ICAD) or if they underwent intra-arterial thrombolysis. Study groups were defined as patients developing vasospasm during EVT (V+) and patients who did not (V−). The study groups were compared in univariable analysis. Multivariable regression models were developed to predict the patient’s risk for developing vasospasm based on pre-identified potential prognostic factors. The secondary endpoint was clinical outcome defined as the modified Rankin Scale (mRS) difference between pre-stroke mRS and discharge mRS (delta mRS) and likelihood of successful reperfusion (TICI 2b/3). Results: In total, 132/1768 patients (7.5%) developed vasospasm during EVT. Vasospasm was more likely to occur in EVT with multiple thrombectomy attempts and after several stent retriever maneuvers. Factors associated with developing vasospasm were younger age (OR = 0.967, 95% CI = 0.96–0.98) and lower pre-stroke mRS (OR = 0.759, 95% CI = 0.63–0.91). The prediction model incorporating patient age, pre-stroke mRS, stent retriever thrombectomy attempts, and total attempts as prognostic factors was found to predict vasospasm with good accuracy (AUC = 0.714, 95% CI = 0.709–0.720). V+ patients showed higher median (IQR) delta mRS (2 (1–4) vs 2 (1–3); p = 0.014). There was no difference in successful reperfusion (TICI 2b-3) between those with or without vasospasm. Conclusion: Vasospasm was a common complication in EVT affecting younger and previously healthy patients. Presence of vasospasm did not reduce the likelihood of successful reperfusion. As independent predictors, patient age, pre-stroke mRS, thrombectomy maneuvers, and stent retriever attempts predict the occurrence of vasospasm during EVT with good accuracy.