Summary Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 provides an up-to-date analysis of the burden of diarrhoea in 195 countries. This study assesses cases, deaths, and aetiologies in 1990–2016 and assesses how the burden of diarrhoea has changed in people of all ages. Methods We modelled diarrhoea mortality with a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We modelled diarrhoea incidence with a compartmental meta-regression tool that enforces an association between incidence and prevalence, and relies on scientific literature, population representative surveys, and health-care data. Diarrhoea deaths and episodes were attributed to 13 pathogens by use of a counterfactual population attributable fraction approach. Diarrhoea risk factors are also based on counterfactual estimates of risk exposure and the association between the risk and diarrhoea. Each modelled estimate accounted for uncertainty. Findings In 2016, diarrhoea was the eighth leading cause of death among all ages (1 655 944 deaths, 95% uncertainty interval [UI] 1 244 073–2 366 552) and the fifth leading cause of death among children younger than 5 years (446 000 deaths, 390 894–504 613). Rotavirus was the leading aetiology for diarrhoea mortality among children younger than 5 years (128 515 deaths, 105 138–155 133) and among all ages (228 047 deaths, 183 526–292 737). Childhood wasting (low weight-for-height score), unsafe water, and unsafe sanitation were the leading risk factors for diarrhoea, responsible for 80·4% (95% UI 68·2–85·0), 72·1% (34·0–91·4), and 56·4% (49·3–62·7) of diarrhoea deaths in children younger than 5 years, respectively. Prevention of wasting in 1762 children (95% UI 1521–2170) could avert one death from diarrhoea. Interpretation Substantial progress has been made globally in reducing the burden of diarrhoeal diseases, driven by decreases in several primary risk factors. However, this reduction has not been equal across locations, and burden among adults older than 70 years requires attention. Funding Bill & Melinda Gates Foundation.