Conclusion: MDM2-309 polymorphism variant genotypes decrease the risk of recurrence in vocal leukoplakia. Objective: The results of a previous study 2 years ago showed the effect of mouse double minute 2 homolog (MDM2) SNP309 polymorphisms in people with laryngeal carcinoma and vocal leukoplakia (a pre-cancerous laryngeal carcinoma lesion). This prospective, clinical trial was performed to assess the relationship between MDM2-309 polymorphism variants and recurrence/cancerization rates in people with vocal leukoplakia over a 2-year period. Participants and method: A total of 61 post-operative patients with vocal leukoplakia participated in this prospective, observational, 2-year, follow-up study, and were genotyped for the MDM2-309 gene using pyrosequencing. Recurrence and cancerization rates were used to assess the relationship between the clinical outcome and the genotype variants. Results: The recurrence rate in the GT genotypes group was lower than that in the normal TT genotype group (17.2% vs 50%, p = 0.05) and there was a significantly lower recurrence rate in the GG genotype group than in the normal TT genotype group (10% vs 50%, p = 0.03). However, there was no statistically significant difference in the cancerization rate between the MDM2-309 variant (GT + GG) genotypes group and the normal TT genotype group (12.2% vs 8.3%, p > 0.05) over the 2-year follow-up period.