Background: There is no consensus on the effect of opium on stroke yet. Some studies show the negative effects of opium on ischemic strokes. Here, we attempt to compare the volume of lesions in opium addict and non-addict patients with thrombotic stroke. Methods: This case-control study was conducted on patients with thrombotic stroke at Shafa Hospital in Kerman, Iran. The diagnosis was confirmed by clinical examinations, imaging, and laboratory tests. The volume of lesions was calculated by magnetic resonance imaging (MRI), and the data were analyzed by descriptive statistics, Mann-Whitney U test, Chi-square test, and linear regression analysis. Findings: A total of 60 patients were studied, 30 of whom were opium addicts and the rest were non-addicts. The mean volume of the lesion was 46.008350 ± 7.488990 (in the addict group) and 31.023335 ± 1.441570 (in the non-addict group), indicating a significant difference between the two groups (P = 0.005). Regression analysis results showed a significant relationship between the volume of stroke with opium addiction (P = 0.017), ischemic heart diseases (IHDs) (P = 0.006), hyperlipidemia (HLP) (P = 0.016), age (P = 0.035), and smoking (P = 0.044). Conclusion: The results of this study showed a higher volume of lesion in opium-addict patients compared to that in non-addicts as an indicator of stroke severity.