Considerable proportions of rice grains produced in some areas in southern China contain high concentrations of cadmium (Cd), leading to unsafe levels of dietary Cd intake. Cultivars of Indica rice, widely grown in southern China, are particularly prone to high Cd accumulation in the grain. Effective methods are needed to decrease Cd accumulation in Indica rice. OsHMA3, encoding a tonoplast Cd transporter, was overexpressed in an elite Indica rice cultivar (Zhongjiazao 17) driven by CaMV 35S promoter. The effects on Cd translocation, accumulation and tolerance, as well as on the agronomic traits and micronutrient concentrations were evaluated. OsHMA3 overexpression markedly decreased Cd translocation from roots to shoots and increased Cd tolerance. OsHMA3 overexpression decreased Cd concentrations in brown rice by 94–98%, to levels just above the detection limit, when rice plants were grown in two Cd-contaminated paddy soils. OsHMA3 overexpression generally had no significant effect on grain yield and the concentrations of the essential micronutrients including zinc, iron, copper and manganese in field trials. Overexpression of OsHMA3 is a highly effective method to reduce Cd accumulation in Indica rice, producing rice grains that were almost Cd free with little effect on grain yield or essential micronutrient concentrations. •High Cd concentrations of Cd are found in some rice produced in southern China.•Transgenic rice overexpressing OsHMA3 gene was developed in an elite Indica cultivar.•Overexpressing OsHMA3 decreased grain Cd concentration by 94–98%.•Overexpressing OsHMA3 had little effect on grain yield and essential micronutrients.