Although ultrasound (US) guidance for venous access is becoming the “standard of care” for preventing access site complications, its feasibility for arterial access has not been fully investigated, especially in the neuro-interventional population. We conducted the first prospective cohort study on US-guided femoral artery access during neuro-interventional procedure. This study included 64 consecutive patients who underwent US-guided femoral artery access through 66 arterial access sites for diagnostic and/or neuro-interventional purposes. The number of attempts required for both the sheath insertion and the success of anterior wall puncture were recorded. In addition, the occurrence of major complications and hematoma formation on the arterial access site examined by US were statistically analyzed. The median number of attempts was 1 (1–2) and first-pass success rate was 63.6%. Anterior wall puncture was achieved in 98.5%. In one case (1.5%), a pseudoaneurysm was observed. In all cases, US clearly depicted a common femoral artery (CFA) and its bifurcation. Post-procedural hematoma was detected in 13 cases (19.7%), most of which were “tiny” or “moderate” in size. Low body mass index and antiplatelet therapy were the independent risk factors for access site hematoma. The US-guided CFA access was feasible even in neuro-interventional procedure. The method was particularly helpful in the patients with un-palpable pulsation of femoral arteries. To prevent arterial access site hematoma, special care should be taken in patients with low body mass index and who are on antiplatelet therapy.