Background: After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Materials and Methods: Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. Results: In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. Conclusions: The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.