Previous research supported that the prevalence of addiction is related to brain laterality. Brain laterality is often determined by left/right handedness and this phenomenon is considered as an important factor in addiction prevalence. The present study attempts to examine the relationships between left/right handedness with addiction and smoking on Iranian population. In this study, 2000 male and female non-addicted (age 31±3 years old) and 1000 male and female addicted (age 42±4 years old) were examined for left/right handedness. The results showed that: right versa left handedness percentages for normal subjects were 91.3% to 8.7% respectively, while for the addict and smoker group were 79.3% to 20.7% respectively. These data indicated that the prevalence of addiction and smoking among left-handed subjects was very higher than right-handed group (P< 0.001). In conclusion, it is clear that the risk of addiction is higher in left-handed individuals, which is consistent with previous studies.