Background: Candidiasis is the most common opportunistic oral infection and smoking is considered as one of its well-known risk factors. However, it remains unknown whether opium users are susceptible to increased oral candida colonization. The aim of the present study is to compare the prevalence rate of oral candida colonization between opium users and cigarette smokers in Kerman, Iran. Methods: This case-control study included 75 healthy male respondents divided into three groups (25 in each group): cigarette smokers, cigarette and opium users, and non-smokers as control group. The samples were obtained from oral mucosa by scraping the mucosa with a sterile cotton swab then inoculated into Sabouraud Dextrose Agar (SDA) and CHROMagar plates and also examined with the light microscope. Findings: Candida was identified in 38.70% of respondents. The most frequently isolated species was Candida albicans (90.66%). The highest prevalence of candida carriage was found in cigarette smokers (52.00%). The difference of candida carriage between the two groups of cigarette smokers and cigarette plus opium users and the control group was statistically significant (P = 0.007 and P = 0.015, respectively). Conclusion: In the present study, it was revealed that the prevalence of oral candida carriage was significantly higher among cigarette and opium users in comparison to the non-users.