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Introduction Mechanical thrombectomy (MT) for medium vessel occlusions (MeVO) is technically challenging due to narrow and tortuous anatomy. While achieving recanalization on the first pass is ideal, multiple attempts are often necessary.Aim of Study We investigated factors contributing to first-pass failure and examined effective second-pass strategies.Method Among 232 MeVO cases treated with MT between January 2018 and December 2023, we analyzed 95 cases where first-pass TICI 2b/3 was not achieved. We evaluated initial techniques, reasons for failure, second-pass strategies, recanalization outcomes, and 3-month mRS by pass number.Results Initial techniques included contact aspiration (48.4%), combined (35.8%), and stent retriever (15.8%). Frequent failure causes were undersized devices (23.1%), poor occlusion visualization (17.9%), small target vessels (12.6%), and thrombus factors (12.6%). Second-pass approaches included technique change (51.6%), same approach (15.8%), deeper aspiration (14.7%), and device upsizing (10.5%), with 83.7% achieving TICI 2b/3. Final TICI 2b/3 was 82.1%. Favorable outcomes occurred in 58.3% (2–3 passes) vs. 30.4% (≥4 passes) (p = 0.0076).Conclusion First-pass failure in MeVO thrombectomy was associated with thrombus and anatomical factors, as well as operator-dependent factors like device selection and positioning. Optimal device choice and tailored technique are key to effective recanalization and better outcomes.Conflict of Interest No