BACKGROUND: Globally, stroke is the second leading cause of death and disability. In different studies conducted previously, the choline-containing phospholipids citicoline and choline alphoscerate have been proposed as adjuvants in the treatment of acute strokes. A systematic review was conducted to provide updated information on the effects of citicoline and choline alphoscerate in patients with acute and hemorrhagic strokes. METHODS: PubMed/Medline, Scopus, and Web of Science were searched to identify relevant materials. Data were pooled, and odds ratios (OR) were reported for binary outcomes. Using mean differences (MD), we evaluated continuous outcomes. RESULTS: A total of 1460 studies were reviewed; 15 studies with 8357 subjects met the eligibility criteria and were included in the analysis. In our study, citicoline treatment did not result in improved neurological function (NIHSS < 1, OR = 1.05; 95% confidence interval (CI): 0.87-1.27) or functional recovery (mRS < 1, OR = 1.36; 95% CI: 0.99-1.87) in patients with acute stroke. Choline alphoscerate improved neurological function and functional recovery in stroke patients based on the Mathew's scale and the Mini-Mental State Examination (MMSE). CONCLUSION: Citicoline did not improve the neurological or functional outcomes in acute stroke patients. In contrast, choline alphoscerate improved neurological function and functional recovery and reduced dependency in stroke patients.