Background: Deep Vein Thrombosis (DVT) is a high-risk condition that necessitates the use of oral anticoagulants for treatment. Warfarin, a common anticoagulant, exhibits varying levels of efficacy and toxicity among individuals. The CYP2C9 gene promoter polymorphism significantly influences the dosage requirements, a factor that remains underexplored in the contemporary Indian population. Objectives: This study aimed to investigate the influence of CYP2C9 gene polymorphisms on warfarin dosage due to pharmacogenetic effects. Specifically, it examined the prevalence of the CYP2C9 polymorphic alleles *2 and *3 and their correlation with warfarin dosage in the South Indian Population (NCAP). Methods: The study involved 96 warfarin-treated patients to determine the genotype frequency of common CYP2C9 polymorphisms. The genotypes of CYP2C92 and CYP2C93 polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A one-way analysis of variance (ANOVA) was conducted to ascertain dosage variation across genotypes. Results: The study found that the frequencies of the two variations were 25.5% for CYP2C92 and 40.6% for CYP2C93. Patients with a homozygous wild-type genotype for CYP2C9 (*1/*1) required a daily warfarin dose of 4.07 ± 1.75 mg, significantly higher than the *1/*2, *1/*3 (2.93 ± 2.03 mg, p <0.0001) and *2/*2, *2/*3, and *3/*3 patients (1.54 ± 1.05 mg, p = 0.002). The study also revealed a distinct allelic frequency of CYP2C9 polymorphisms in the study population compared to other populations. Conclusion: Given the relatively high prevalence of CYP2C9 polymorphisms in the studied population, practitioners should consider these findings to minimize the risk of bleeding when prescribing warfarin. © 2024 Elsevier B.V., All rights reserved.