The number of Plasmodium vivax malaria patients in the Republic of Korea and North Korea since the re-emergence of malaria in 1993 is estimated to be approximately one million. To cope with this situation, the Army of the Republic of Korea has performed chemoprophylaxis with hydroxychloroquine and primaquine since 1997. The cumulative number of soldiers in the Army of the Republic of Korea given chemoprophylaxis exceeded 1.4 million by 2007. Extensive chemoprophylaxis contributed to preventing a rapid increase of malaria patients in the Army of the Republic of Korea, but increased the possibility of the occurrence of chloroquine (CQ)-resistant P. vivax strains. In this study, treatment responses of P. vivax malaria patients in the Republic of Korea monitored during 2003-2007, and CQ resistance was confirmed in 2 of 484 enrolled patients. Our results are the first report of CQ-resistant P. vivax in a temperate region of Asia. Continuous surveillance is warranted to monitor the change in CQ resistance frequency of P. vivax in the Republic of Korea.