Background: Atrial fibrillation (AF) is associated with poorer functional outcomes in acute stroke patients. It has been hypothesized that this is due to poor collateral recruitment. Aims: This study aimed to investigate the relationship between AF and collaterals with outcome in thrombectomy patients. Methods: This retrospective cohort study identified 1036 acute ischemic patients from the INternational Stroke Perfusion Imaging REgistry. The cohort was divided into two groups: 432 with AF and 604 without AF. Patients were stratified by collateral grades as good, moderate, and poor. Within each collateral grade, the prediction of AF versus No AF for good outcome (3-month modified Rankin Scale of 0–2) was determined. Then, within each collateral grade, perfusion was compared between those with and without AF. Results: AF was negatively associated with good outcome in patients with poor collaterals (26.7% vs 51.2% for AF vs No AF, odds ratio = 0.32 (95% confidence interval = 0.22–0.50), p < 0.001), but not in patients with good (50.9% vs 58.1% for AF vs No AF, odds ratio = 0.75 (0.46–1.23), p = 0.249) or moderate collaterals (43.6% vs 50.9% for AF vs No AF, odds ratio = 0.75 (0.47–1.18), p = 0.214). AF was associated with severe hypoperfusion only in patients with poor collateral flow (54.0 vs 35.5 mL for AF vs No AF, p < 0.001). Conclusions: AF-related stroke is associated with more severe hypoperfusion and worse outcome in those with poor collaterals.