Arsenic (As) methylation is an important component of As biogeochemical cycle. Microbial As methylation is enhanced under anoxic conditions in paddy soil, producing dimethylarsenate (DMA) which can cause physiological straighthead disease in rice. We conducted field experiments at two sites to test the effect of midseason draining of paddy water on microbial As methylation and the incidence of straighthead disease. Compared to continuous flooding, midseason draining increased soil Eh, decreased the abundances of microbial genes for arsenate reduction (arsC and arrA) and arsenite methylation (arsM), and lowered the concentrations of both inorganic As and DMA in soil porewater. Draining shifted microbial composition, resulting in decreases in the relative abundance of 17-132 amplicon sequence variants. Draining decreased the accumulation of DMA in rice husk and of inorganic As and DMA in rice grain, decreased the incidence of straighthead disease, and increased grain yield by 20-45 %. Further experiments were conducted at eight field sites to assess the effect of midseason draining in a split field design. Draining decreased husk DMA concentration by 40-65 % and increased grain yield by 25-209 %. This study demonstrates that midseason draining can effectively suppress microbial As methylation and alleviate rice straighthead disease, benefiting both grain yield and safety.