Background The optimal first-line mechanical thrombectomy (MT) method in cancer-related stroke (CRS) patients with emergent large vessel occlusion (ELVO) remains largely unknown. The aim of this study is to evaluate the efficacy and safety between contact aspiration (CA) first-line thrombectomy and stent retriever (SR) first-line thrombectomy in CRS patients. Methods Sixty-two CRS patients with ELVO, who underwent MT between January 2013 and October 2019 at our institution, were retrospectively analyzed. Patients were divided into two groups based on the first-line MT method and compared: the CA group (n=28), which included those who received CA alone or combined CA with SR, and the SR group (n=34), which included those who received conventional SR alone. Results Overall, reperfusion was successful in 75.8% (47/62) of CRS patients, and a good clinical outcome at 90 days was observed in 17.7%. The CA group showed a higher rate of successful reperfusion (89.3% vs 64.7%, P=0.025) shorter procedure time (22 vs 42 min; P=0.029), higher rate of first pass effect (35.7% vs 11.8%, P=0.025), and lower number of passes (1 vs 3, P=0.023) when compared with the SR group. The procedural and hemorrhagic complication rates were similar between the CA and SR groups. The first-line contact aspiration (OR 11.624, 95% CI 1.041 to 129.752; P=0.046) was an independent predictor of successful reperfusion. Conclusions Among patients with CRS, CA - whether alone or in combination with SR - as first-line MT seems to provide more rapid and successful reperfusion when compared with SR.