Purpose <p>To evaluate one- and two-year outcomes of genicular artery embolization (GAE) using 200-µm permanent microspheres in patients with symptomatic knee osteoarthritis (KOA) and identify predictors of clinical response. Long-term GAE outcome data are sparse but necessary to understand durability of the intervention.</p> Material and Methods <p>&#xa0;A single-center, IRB-approved retrospective study including 34 consecutive patients received GAE for symptomatic KOA from September 2021 to January 2024. GAE was performed using 200-µm polyethylene glycol microspheres. Clinical outcomes were assessed with the&#xa0;Ontario and McMaster Universities Osteoarthritis Index (WOMAC)&#xa0;scoring system at pre-GAE visit and up to 2 years post-GAE. A 20% reduction in the WOMAC pain score at 1 and 2 years was considered clinically significant as well as by the OARSI-Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology criteria (OMERACT). Kaplan–Meier analysis was performed to investigate clinical response over time. Univariate and multivariate analysis was performed for gender, race, age, BMI, vessels treated, embolic volume, Kellgren–Lawrence (KL) grading using Fisher and t-tests.</p> Results <p>Thirty-four patients and 42 knees were treated with KOA severity: KL3 ≥ 90%. One-year proportion of clinical response by MCID: 23.8% (95% CI 13.9–40.9) and by OMERACT: 21.4% (95% CI 12.0–38.2). Two-year proportion of clinical response by MCID: 19.8% (95% CI 10.4–38.0) and by OMERACT: 16.1% (95% CI 7.2–36.1). Adverse event rate was 30.1%. BMI was predictive of categorical response (univariate: <i>P</i> = 0.012 and multivariate: <i>P</i> = 0.033).</p> Conclusion <p>GAE using 200-µm PEG microspheres shows modest long-term outcomes for KOA with acceptable safety profile.</p> Graphical Abstract <p></p>