Background and Objective: Evidence is indicative of the positive effect of citicoline administration in stroke patients; however, there are controversies over this issue. Regarding this, the present study was conducted to investigate the efficacy of citicoline in acute stroke patients. Materials and Methods: This randomized clinical trial was conducted on 160 patients with hemorrhagic and ischemic stroke. The participants were randomly assigned into two groups of intervention and control. The intervention group daily received 1 g citicoline injections for 10 days, in addition to the standard therapy. The baseline severity of the disease was determined by the National Institutes of Health Stroke Scale, and the outcome of the disease was assessed using the Modified Rankin Scale and Barthel Index on the 1 st , 10 th , and 90 th days post-intervention. Statistical analysis was performed using Stata software (version 11.1). P-value less than 0.05 was considered statistically significant. Results: According to the results, there was no significant difference between the two groups in terms of gender, mean age, hypertension, diabetes, smoking, hyperlipidemia, and mortality after stroke (P>0.05). Regardless of the type of stroke, the severity of the disease decreased over time in both groups. However, at the end of the study (the 90 th day), the intervention group had lower disease severity, compared to the control group (P<0.05). In terms of the ischemic stroke patients, the severity of the disease was significantly lower in the intervention group on the 90 th day, compared to that in the control group. Conclusion: Based on the findings of this study, the use of citincoline in acute stroke patients exerted no significant effect in the disease treatment in the short term. However, the long-term administration of this medication could result in significant impacts on the treatment of the patients, especially those with ischemic stroke, and improvement of their efficacy.