Objective To quantify radiation exposure (RE) of endovascular stroke treatment (EST) in the anterior circulation per thrombectomy attempt and determine causes for interventions associated with high RE. Methods A retrospective single-center study of an institutional review board−approved stroke database of patients receiving EST for large vessel occlusions in the anterior circulation between January 2013 and April 2018 to evaluate reference levels (RL) per thrombectomy attempt. ESTs with RE above the RL were analyzed to determine causes for high RE. Results Overall, n = 544 patients (occlusion location, M1 and M2 segments of the middle cerebral artery 53.5% and 27.2%, carotid artery 17.6%; successful recanalization rate 85.7%) were analyzed. In the overall population, DAP (in Gy cm 2 , median (IQR)) was 113.7 (68.9-181.7) with a median fluoroscopy time of 31 min (IQR, 17-53) and a median of 2 (IQR, 1-4) thrombectomy attempts. RE increased significantly with every thrombectomy attempt (DAP 1 , 68.7 (51.2-106.8); DAP 2 , 106.4 (84.8-115.6); p value 1vs2 , < 0.001; DAP 3 , 130.2 (89.1-183.6); p value 2vs3 , 0.044; DAP 4 , 169.9 (128.4-224.1); p value 3vs4 , 0.001; and DAP 5 , 227.6 (146.3-294.6); p value 4vs5 , 0.019). Procedures exceeding the 90th percentile of the attempt-dependent radiation exposure level were associated with procedural complications (n = 17/52, 29.8%) or a difficult vascular access (n = 8/52, 14%). Conclusions Radiation exposure in endovascular stroke treatment is depending on the number of thrombectomy attempts. Radiation exposure doubles when three attempts and triples when five attempts are necessary compared with single-maneuver interventions. Procedural complications and difficult vascular access were associated with a high radiation exposure in this collective. Key Points • Radiation exposure of endovascular stroke treatment (EST) is dependent on the number of thrombectomy attempts. • Reference levels as means for quality control in hospitals performing endovascular stroke treatment should be defined by the number of thrombectomy attempts-we suggest 107 Gy cm 2 , 156 Gy cm 2 , 184 Gy cm 2 , 244 Gy cm 2 , and 295 Gy cm 2 for 1 to 5 maneuvers, respectively, for EST of the anterior circulation • Cases with high rates of radiation exposure are associated with periprocedural complications and difficult anatomical access as a probable cause for a high radiation exposure.