Golden standard of acute stroke treatment is recanalisation therapy. However, opening the occluded blood vessel sometimes does not show the expected clinical result or leads to haemorrhagic complications. As neuroinflammation and neurotoxicity play an important role in the pathophysiology of stroke, neuroprotective agents might preserve brain tissue after futile recanalisation. After recanalisation therapy and not later than 24 h after symptoms onset, patients with initial NIHSS of ≥ 8 were assigned to the investigational and control group. The investigational group received intravenous Cerebrolysin as add-on therapy. The primary objective was to assess the clinical efficacy of Cerebrolysin. The secondary objective was to investigate its effect on haemorrhagic transition and to confirm its safety profile. Baseline characteristics of patients showed no significant differences between the two groups. No difference could be detected between the two groups in the mRS scale though the Cerebrolysin group showed descriptive superiority over the control group. We found a statistically significant difference considering haemorrhagic transition and mortality rate in favour of the Cerebrolysin group. The multimodal neurotrophic agent Cerebrolysin holds promise to impact on the late consequences of a reperfusion syndrome. Its influence on reducing neuroinflammation, promoting neuronal cell viability and neurogenesis as well as the stabilising effect on the blood-brain barrier suggests a protective effect on the neurovascular unit even when no recanalisation occurs. We confirmed the excellent safety profile of Cerebrolysin. Cerebrolysin as add-on therapy might be beneficial and safe for patients with acute stroke in terms of lowering risk for haemorrhagic complications after recanalisation therapy. •Recanalisation therapy is golden standard of acute stroke treatment.•Neuroprotective agents might preserve brain tissue after futile recanalization.•Cerebrolysine as a multimodal neurotrophic agent can impact the late consequences of a reperfusion injury.•Cerebrolysin may reduce the risk for haemorrhagic complications after recanalisation therapy.