Background: Randomized controlled trials have demonstrated an improved outcome of basilar artery occlusion (BAO) with endovascular thrombectomy (EVT) compared to best medical treatment. However, a minority of the patients recruited up to 12–24 h from onset in the positive trials received intravenous thrombolysis (IVT), and a trial with a higher IVT rate did not show superiority of EVT. Thus, the efficacy and safety of EVT compared to IVT for BAO remain less clear. Aims: We aimed to compare outcomes after IVT alone to EVT with or without IVT for acute BAO. Methods: This international, observational, retrospective study included patients who received recanalization therapy for BAO at six centers between January 2010 and March 2024. The primary outcome was 3-month modified Rankin Scale (mRS) score 0–3, and secondary outcomes comprised mRS 0–2, ordinal mRS, mortality, and symptomatic intracranial hemorrhage. Outcomes after IVT versus EVT ± IVT were compared using inverse probability-weighted regression adjustment models adjusting for known predictors of outcome in BAO and baseline variables differing between the treatment groups. Interaction of the treatment group with symptom severity and onset-to-treatment time was tested. Results: Of 523 patients with BAO (median age 69, 35.2% women), 28.9% received IVT and 71.1% EVT ± IVT. The IVT-alone group had a lower baseline National Institutes of Health Stroke Scale score (median 11 vs 15) but equally extensive ischemic changes in baseline imaging. After inverse probability-weighted regression adjustment, the IVT-alone group had higher odds of mRS 0–3 (adjusted odds ratio (aOR) = 2.33 [95% confidence interval (CI) = 1.31–4.12]), mRS 0–2 (aOR = 1.93 [95% CI = 1.12–3.30]), lower median mRS (aOR = 1.81 [95% CI = 1.21–2.71]), and lower mortality (aOR = 0.53 [95% CI = 0.29–0.97]), but no difference in symptomatic intracranial hemorrhage (aOR = 0.81 [95% CI = 0.28–2.36]). No interactions for the primary outcome were found. Conclusion: In this study, patients with BAO had better outcome after IVT than EVT ± IVT independent of symptom severity and time from onset. Although the non-randomized design of the study warrants caution, the results encourage further trials comparing EVT and IVT to guide recanalization therapy in BAO patients. Data access statement: Anonymized data are available upon reasonable request to the corresponding author following the national legislation.