Background While recent studies suggest a benefit of mechanical thrombectomy (MT) for the treatment of patients with isolated large vessel occlusions presenting after 24 hours from the last known well (LKW), the effect of MT for acute cervical tandem lesions (TLs) beyond 24 hours remains unknown. We aimed to evaluate the safety and effectiveness of MT beyond 24 hours of LKW in patients with TLs. Methods We conducted a subanalysis study of patients with anterior circulation TL enrolled in a large, multicenter registry between January 2015 and December 2020. Patients were divided into 2 groups: MT beyond 24 hours versus MT 0–24-hour window. Outcomes of interest were functional independence (90-day modified Rankin scale 0-2), complete reperfusion (modified thrombolysis in cerebral infarction 3), delta NIH Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), parenchymal hematoma 2 (PH2), in-hospital mortality, and 90-day mortality. Inverse probability of treatment weighting (IPTW) was used to balance the groups. Results Overall, 589 participants were included, with 33 treated beyond 24 hours and 556 treated in the 0–24-hour window. After IPTW, we found no significant difference in the rates of achieving functional independence (odds ratio (OR) = 0.51; 95% confidence interval (CI) 0.22–1.16; p = 0.108), complete reperfusion (OR = 1.35; 95% CI 0.60–3.05; p = 0.464), sICH (OR = 1.96; 95% CI 0.37–10.5; p = 0.429), delta NIHSS (β = −3.61; 95% CI −8.11 to 0.87; p = 0.114), PH2 (OR = 1.46; 95% CI 0.29–7.27; p = 0.642), in-hospital mortality (OR = 1.74; 95% CI 0.52–5.86; p = 0.370), or 90-day mortality (OR = 1.37; 95% CI 0.49–3.83; p = 0.544) across both time windows. Conclusions Our results suggest that MT appears to benefit patients with TLs beyond 24 hours from LKW. Future prospective studies are warranted.