To determine the burden and distribution of acute gastrointestinal illness (AGI) in the population, a cross-sectional, monthly face-to-face survey of 10 959 residents was conducted in Jiangsu province between July 2010 and June 2011. The adjusted monthly prevalence was 4·7% with 0·63 AGI episodes/person per year. The prevalence was the highest in children aged <5 years and lowest in persons aged ⩾65 years. A bimodal seasonal distribution was observed with peaks in summer and winter. Regional difference of AGI prevalence was substantial [lowest 0·5% in Taicang, highest 15·1% in Xinqu (Wuxi prefecture)]. Healthcare was sought by 38·4% of the ill respondents. The use of antibiotics was reported by 65·2% of the ill respondents and 38·9% took antidiarrhoeals. In the multivariable model, gender, education, season, sentinel site and travel were significant risk factors of being a case of AGI. These results highlight the substantial burden of AGI and the risk factors associated with AGI in Jiangsu province, China.