Background: Malaria is still considered as a major health problem in the world including in Indonesia, which is regarded as one of the malaria-endemic countries. Since 2006, WHO has recommended the use of artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria. In Indonesia, DHP tablet (combination of dihydroartemisinin and piperaquine) is the first line therapy used in malaria control program, which currently used imported DHP tablet. To produce generic DHP tablet, comparative bioequivalence test between DHP tablet and the drug previously used is needed. Methods: A single dosed, randomized, double-blinded, one-period, and parallel study design was conducted in the present research. Every twenty-four subjects were assigned into two groups, which are test group and comparison group. Results: The results showed that even though in vitro comparison of dissolution test has fulfilled the requirements, in vivo test results has not fulfilled the bioequivalence standards. Obtained geometric mean ratios (90% confidence intervals) of the test drug to comparator drug for dihydroartemisinin were 83.30% (67.06%â€“103.48%) for AUC0-t, 83.24% (67.10%â€“103.26%) for AUC0-inf, and 75.67% (61.83%â€“92.61%) for Cmax. The geometric mean ratios (90% confidence intervals) of the test drug to comparator drug for piperaquine were 97.31% (76.50%â€“123.80%) for AUC0-t, 94.18% (74.18%â€“119.59%) for AUC0-inf, and 96.47% (71.80%â€“129.62%) for Cmax. Conclusions: Therefore, the pharmacokinetic profile of the test drug is concluded to be bio-inequivalent with the comparator drug.