Objective: To describe the epidemiology of illness at the Rio 2016 Summer Paralympic Games. Methods: A total of 3657 athletes from 78 countries, representing 83.5% of all athletes at the Games, were monitored on the WEB-IISS over 51, 198 athlete days during the Rio 2016 Summer Paralympic Games. Illness data were obtained daily from teams with their own medical support through the WEB-IISS electronic data capturing systems. Results: The total number of illnesses reported was 511, with an illness incidence rate (IR) of 10.0 per 1000 athlete days (12.4%). The highest IRs were reported for wheelchair fencing (14.9), Para swimming (12.6) and wheelchair basketball (12.5) (p < 0.05). Female athletes and older athletes (35-75 years) were also at higher risk of illness (both p < 0.01). Illnesses in the respiratory, skin and subcutaneous and digestive systems were the most common (IRs of 3.3, 1.8 and 1.3, respectively). Conclusion: The medical data recorded on the WEB-IISS in this study show that 1) the rate of illness was lower than that reported for the London 2012 Summer Paralympic Games, 2) the sports with the highest risk were wheelchair fencing, Para swimming and wheelchair basketball, 3) female and older athletes (35-75 years) were at increased risk of illness, and 4) the respiratory system, skin and subcutaneous system and digestive system were most affected by illness. These results would allow for comparative data to be collected at future editions of the Games and can be used to inform illness prevention programs.