Background/Objectives: Collateral development after AIS is important for prognosis and treatment. In this study, we aimed to investigate the relationship and correlation between biochemical parameters and CT angiography collateral score within the first 9 h and its effect on the neurological outcomes of patients with AIS due to MCA infarction. Methods: A total of 98 patients with MCA infarction were hospitalized for diagnosis and treatment after undergoing CT angiography within 9 h of suffering a stroke. Demographic data, admission biochemical parameters, hospitalization data, and discharge NIHSS scores were recorded. Souza's scoring system for collateral distribution was used to evaluate collaterals. Souza CS system and clinical disability comparison outcomes identified. Results: According to the Souza CS system, 13 patients were in the malignant profile category, and 85 patients were in the good profile category. The NIHSS value of patients with a malignant profile was 27, while the mean NIHSS value of patients with a good profile was 9. There was a statistically significant difference in uric acid, total cholesterol, triglyceride, HDL cholesterol, CRP, hsCRP, D-Dimer, troponin I, vitamin B12, fibrinogen, NSE, homocysteine, aPTT, and INR levels according to collateral distribution. Conclusions: This study demonstrates that biochemical parameters can influence the distribution of malignant and benign collaterals in AIS independent of age and gender.