Background Large anterior choroidal artery (AChA) infarcts are frequently associated with stroke evolution. This study aimed to investigate the major determinants for stroke evolution in patients with large AChA infarcts. Methods We studied 118 consecutive adult patients with acute large AChA infarcts. The diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted imaging within typical AChA vascular regions. Stroke evolution was defined as neurologic deterioration with an increase in National Institutes of Health Stroke Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function by at least 2 in 7 days after stroke onset. Results Forty-seven (39.8%) patients developed stroke evolution. Thrombolytic therapy was inversely associated with the occurrence of stroke evolution ( P  = .004). Using multivariate analysis, thrombolytic therapy was the only protective determinant for stroke evolution (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term functional outcome than those not receiving thrombolytic therapy (adjusted odds ratio, .11; 95% confidence interval, .02-.75). Conclusions Thrombolytic therapy is an only determinant factor for stroke evolution in large AChA infarcts, which reduced the risk of stroke evolution and improved functional outcome.