Introduction: Malaria is one of the major public health problem in South East Asian & African countries especially in India. This is a protozoan disease transmitted by a vector i.e. female anopheles mosquito. The prevalent species of malarial parasite are plasmodium vivax and falciparum. The present study has been undertaken to evaluate the efficacy of various drugs chloroquine, quinine, doxycycline and artimisinin (artesunate) combined therapy (ACT) in uncomplicated vivax and falciparum malarial infection. Material and Methods: A total of 120 hospitalized patients (smear positive cases 60 each of P. vivax (group A) and P. falciparum or mixed malaria (Group B)) of medical wards (including elderly age group also) in Dr. D.Y. Patil Medical College and Hospital, Navi Mumbai, were included. Complicated cases were excluded which had target organ damage. Complete blood count and parasitic index were done on day I, 4 and 7 in addition to liver, kidney, pulmonary and cardiac functions. Results: The observations revealed that patients of group A responded early to treatment as compared to group B regarding fever and parasitic index disappearance. The group A did respond partially and statistically significant to chloroquine than to other drugs combinations whereas group B did not respond satisfactorily to chloroquine but had reasonable statistically significant effect to other drugs Conclusions: The best medications were artesunate and quinine in combination with doxycycline in both the groups A and B whereas chloroquine with doxycycline did not fare well in either group. Thus the artesunate combination therapy (ACT) is emerging as the first line treatment in drug resistant malaria under present circumstances.