Changes in human lifestyle and food consumption have resulted in a large increase in the incidence of type-2 diabetes, obesity and colon disease especially in Asia. These conditions are a growing threat to human health, but consumption of foods high in resistant starch (RS) can potentially reduce their incidence. Strategies to increase RS in rice are limited by a lack of knowledge of its molecular basis. Through map-based cloning of a new RS locus in indica rice, we have identified a defective soluble starch synthase gene (SSIIIa) responsible for RS production, and further showed that RS production is dependent on the high-expression of the Waxy^a allele which is prevalent in indica varieties. The resulting RS has modified granule structure, high amylose, lipid and amylose-lipid complex, and has altered physico-chemical properties. This discovery provides an opportunity to increase RS content of cooked rice especially in the indica varieties which predominate in southern Asia.