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To determine the efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels. Totally 96 cases of acute cerebral infarction (ACI) patients without clear criminal vessels enrolled in our hospital from July 2017 to July 2020 were randomized to the control group (n=48) with urokinase (n=48) and the observation group (n=48) with urokinase and tirofiban. Clinical efficacy, National Institute of Health Stroke Scale (NIHSS) score, Barthel Index (BI), Clusterin (CLU), tumor necrosis factor-α (TNF-α), serum hypersensitive C-reactive protein (hs - CRP), interleukin-6 (IL-6) and safety were compared. The observation group outperformed the control group in terms of clinical efficacy. Before treatment, the NIHSS scores, BI scores and serum levels of CLU, TNF-α, hs - CRP, and IL-6 in the control group were similar to those in the observation group. After treatment, the above indicators were all decreased, and lower in the observation group. The observation group had a lower incidence of adverse reactions. Arterial thrombolysis of urokinase plus tirofiban in ACI patients without clear responsible vessels effectively reduces postoperative NIHSS score, improves self-care ability, relieves the level of inflammatory factors, with fewer adverse reactions and higher safety profile.