Background <p>Futile recanalization (FR) is a common and challenging phenomenon in acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). This study aimed to demonstrate the relationship of neutrophil to high-density lipoprotein ratio (NHR) and FR in AIS patients.</p> Methods <p>AIS patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia (mTICI) score 2b–3) after MT were retrospectively analyzed. Futile recanalization was defined as modified Rankin scale (mRS) score 3–6 at 90 days even with successful recanalization. Locally estimated scatterplot smoothing (LOESS) and piecewise-linear models were conducted to investigate the association between NHR and FR.</p> Results <p>A total of 877 patients were included in the analyses and 487 (55.53%) of them experienced FR at 90-day follow-up. An approximate J-shaped association was detected between NHR levels and FR. When NHR levels were below 3.25, there was no evidence of association between NHR and FR. While NHR levels ranged from 3.25 to 10.65, a 1-unit increase in the NHR level was associated with a 13% decreased OR of FR (adjusted OR: 0.87; 95%CI: 0.79 to 0.96; <i>P</i> = 0.006). However, when NHR levels were over 10.65, a 1-unit increase in the NHR level was associated with a 30% greater adjusted OR of FR (OR: 1.30; 95%CI: 1.01 to 1.67; <i>P</i> = 0.041).</p> Conclusion <p>Our findings suggest that NHR may be a potential biomarker for FR, and provide new insights into the mechanisms of FR.</p>