Abstract Purpose In mechanical thrombectomy, it has been hypothesized that multiple retrieval attempts might the improve reperfusion rate but not the clinical outcome. In order to assess a potential harmful effect of a mechanical thrombectomy on patient outcome, the number of retrieval attempts was analyzed. Only patients with a thrombolysis in cerebral infarction (TICI) score of 0 were reviewed to exclude the impact of eventual successful reperfusion on the mechanical hazardousness of repeated retrievals. Methods In this study 6635 patients who underwent endovascular thrombectomy (EVT) for acute large vessel occlusion (LVO) from the prospectively administered multicenter German Stroke Registry were screened. Insufficient reperfusion was defined as no reperfusion (TICI score of 0), whereas a primary outcome was defined as functional independence (modified Rankin scale [mRS] 0–2 at day 90). Propensity score matching and multivariable logistic regressions were then performed to adjust for confounders. Results A total of 377 patients (7.8%) had a final TICI score of 0 and were included in the study. After propensity score matching functional independence was found to be significantly more frequent in patients who underwent ≤ 2 retrieval attempts (14%), compared to patients with > 2 retrieval attempts (3.9%, OR 0.29, 95% CI 0.07–0.73, p = 0.009). After adjusting for age, sex, admission NIHSS score, and location of occlusion, more than two retrieval attempts remained significantly associated with lower odds of functional independence at 90 days (OR 0.2, 95% CI 0.07–0.52, p = 0.002). Conclusion In patients with failure of reperfusion, more than two retrieval attempts were associated with a worse clinical outcome, therefore indicating a possible harmful effect of multiple retrieval attempts.