Since 2010, malaria rapid diagnostic tests (RDTs) are widely used to detect malaria. The Indian Council of Medical Research-National Institute of Malaria Research performed lot testing (LT) according to WHO procedures since 2016. Lot testing is performed to evaluate the lot-to-lot variation in performance of malaria RDTs. Four sets of positive quality control (QC) panels for P. falciparum (Pf) and P. vivax (Pv) and 10 negative panels tested RDTs. RDTs were reported as pass, failed, or deferred on the basis of WHO criteria. In the past 5 years, 275 lots containing 15,488 RDT kits for malaria diagnosis were subjected to LT. The monovalent RDTs (n = 1,216), based on either Pf histidine rich protein 2 (HRP2) or Pan-Plasmodium lactate dehydrogenase (Pan-pLDH) antigens, showed 90.4% sensitivity and 100% specificity, whereas RDTs based on HRP2 + Pan-pLDH or HRP2 + pLDH (n = 13,924) had sensitivity 95.6% and specificity 99.5%, respectively. RDTs based on PfHRP2 + Pv-pLDH + Pan-pLDH (n = 348) had 100% sensitivity and specificity. In a comparison between HRP2 + pLDH or HRP2 + Pan-pLDH to HRP2 + pLDH + Pan-pLDH RDTs, it was found that the sensitivity of PfHRP2 with Pan-pLDH RDTs (n = 2,382) was only 83%. Of the 275 lots analyzed, 15 lots of PfHRP2 with Pan-pLDH were deferred. The QC panel for Pf revealed a faint Pan band in the tested lots, which is a cause for concern. The results of deferred lots were reported to concerned government agencies. Quality-compromised RDTs may lead to an incorrect diagnosis. It is critical to have a QC system in place for effective malaria management.