Malaria is one of the major causes of morbidity and mortality in Orissa. The present study was undertaken to measure the contribution of chloroquine (CQ) drug-resistant parasites to the risk of severe malaria and their biological advantage in this part of the country. Totally 79 uncomplicated and 93 severe malaria cases were selected according to the WHO criteria. The drug-resistance property was assessed using molecular markers (pfcrt K76T and pfmdr1 N86Y)and multiplication rates of the parasites were measured in the first cycle of in vitro culture. The study reveals that a significant number of severe malaria cases in our study population harbour CQ drugresistant parasites, indicating treatment failure. Further, the association of fatal severe malaria with wildtype parasites and no difference in in vitro multiplication potential between wild and mutant-type parasites causing severe malaria have been discussed in the light of the virulence of the parasite populations found in this epidemiological setting.