We investigated the prevalence of drug-resistant variants and assessed their severity against antiretroviral drugs among patients in South Korea. Three hundred antiretroviral drug-naive patients were collected and drug-resistant variants were analyzed using the Stanford database with sequences and mutation data of the HIV-1 genes for protease (codons 1-99) and reverse transcriptase (codons 1-250). Of this group, 199 isolates (66.3%) showed at least 1 or more sites related to drug resistance. However, the average prevalence of drug resistance for patients newly diagnosed with HIV-1 but still treatment-naive between 1999 and 2005 was very low (4.3%, by "SIR" interpretation) compared with other countries. Most of the newly infected patients carried HIV subtype B (96%, n = 288) based on phylogenetic analysis of the conserved pol region. In summary, there has been no significant increase in the prevalence of drug resistance among antiretroviral drug-naive patients infected with HIV-1 for the last 7 years in South Korea. This study is quite significant regarding its larger scale of prevalence study for drug-resistant variants comparing to other drug-resistant studies using small scale of populations in South Korea. It is also important to provide suitable guidelines of genotyping assays for Korean drug-naive patients.