We report four cases of complicated malaria in Andhra Pradesh-Orissa border between July 2016 and December 2016, with apparent treatment failure with artemisinin drugs, and all showing parasitological clearance after quinine and adjuvant clindamycin therapy. However, one case died due to complications of malaria. We highlight the need for increased monitoring and surveillance to identify artemisinin combination therapy resistance in other parts of India apart from Northeastern states. It is also essential to ensure rationale use of the existing antimalarial drugs.