Reinke's edema (RE) is a benign pathological non-inflammatory disorder of the vocal folds with a wide range of clinical manifestations. We aim to investigate the relationship between Reinke's edema and some common inhalant abuse. In this case-control study, subjective consisted of 23 patients with RE (the cases), and 50 patients with sinusitis (control) who underwent surgery in the Department of Otolaryngology, between 2015 and 2020. Demographic characteristics, history of some related disease, methods, and the duration of cigarette, and opium consumption were collected through the patients' files. The chi-square (χ²) test was run to analyze the differences in the categorical and, and the Independent Sample T-test was used to compare two sample means from unrelated groups. A significant level (p-value) was considered less than 0.05. The mean age was 54 ± 12 years, and 42 ± 11 years, respectively for Reinke's edema and sinusitis. More women had been recorded in the RE group, compared to men. Allergy, unprincipled use of voice and talkativeness, history of laryngeal surgery, and type of disease were correlated to RE (p < 0.05). Also, cigarette smoking was significantly correlated with Reinke's edema. The average number of cigarettes per day, the duration of smoking, and opium consumption were more frequent in RE (P < 0.05). 90% of the RE and 4% of sinusitis patients were opium consumers. There was a statistically significant difference in the methods of substance use in the two groups of cases and control (p < 0.0001). Among the different methods, the poker and stone method was the most common (69.6%), and the opium smoking pipe was the second most common method. This study also confirmed the hazardous effects of smoking and inhaling opiates in the formation of lesions of the pharynx and larynx. In particular, longer use of these substances will be associated with more serious side effects. Therefore, it seems that people who are addicted to opiates should undergo periodic visits and counseling to reduce and stop their use.