Background: The incidence and factors associated with illness in Paralympic athletes have not been documented. Aim: To determine the factors associated with illness in athletes participating in the London 2012 Paralympic Games. Methods: A cohort of 3565 athletes from 160 of the 164 participating countries in the London 2012 Paralympic Games were followed over a 14-day period (precompetition period=3 days, competition period=11 days; 49 910 athlete-days). Daily illness data were obtained from (1) teams with their own medical support who completed a daily illness log (78 teams, 3329 athletes) on a novel web-based system and (2) teams without their own medical support through the local organising committee database (82 teams, 236 athletes). Illness information from all athletes included age, gender, type of sport and the main system affected. Main outcome measurement: Incidence rate (IR) of illness (illness per 1000 athlete-days) and factors associated with IR (time period, gender, age and sport). Results: The IR of illness was 13.2 (95% CI 12.2 to 14.2). The highest IR of illness was in the respiratory system, followed by the skin, digestive, nervous and genitourinary systems. The IR in the precompetition period was similar to that in the competition period, but the IR was significantly higher in athletics compared with other sports. Age and gender were not independent predictors of illness. Conclusions: Illness is common in Paralympic athletes and the main factor associated with higher IR of illness was the type of sport (athletics).