Objective: Intravenous tissue plasminogen activator (IV t-PA) is commonly used as bridging therapy before mechanical thrombectomy (MT) in acute ischemic stroke. However, in practice, some patients undergo MT only after IV t-PA has been fully administered. This study aimed to compare clinical and radiological outcomes of MT only versus IV t-PA followed by MT within 4.5 hours of symptom onset. Methods: We retrospectively reviewed 190 patients with acute large artery occlusion treated with MT between January 2018 and December 2020. After excluding 53 patients ineligible for IV t-PA. A total of 137 patients were enrolled and categorized into two groups: MT only (n=82, 59.8%) and post-IV t-PA MT (n=55, 40.2%). The primary outcome was successful recanalization; the secondary outcome was a good clinical outcome at 90 days (3-month modified Rankin Scale (mRS) score of 0–2). Results: The successful recanalization rates did not significantly differ between the MT-only and post-IV t-PA MT groups (92.7% vs. 89.1%, p=0.466). Good outcomes at 90 days were not statistically different between both groups (58.5% vs. 61.8%, p=0.701). Multivariable analysis identified baseline National Institutes of Health Stroke Scale (NIHSS) score (adjusted odds ratio (OR) 0.873; 95% confidence intervals (CI), 0.806–0.946; p<0.001) and door-to-puncture time (adjusted OR 0.987; 95% CI, 0.978–0.997; p=0.009) as independent predictors of outcome. Conclusions In our study, MT alone yielded comparable outcomes to IV t-PA followed by MT in patients treated within 4.5 hours. Direct MT may be a reasonable treatment strategy.