Although the involvement of common childhood infections in the aetiology of acute appendicitis has long been conjectured, supporting evidence is largely restricted to a disparate set of clinical case reports. A systematic population-based analysis of the implied comorbid associations is lacking in the literature. Drawing on a classic epidemiological dataset, assembled by the School Epidemics Committee of the United Kingdom's Medical Research Council (MRC) in the 1930s, this paper presents a historical analysis of the association between termly outbreaks of each of six common childhood infections (chickenpox, measles, mumps, rubella, scarlet fever and whooping cough) and operated cases of acute appendicitis in 27 English public boarding schools. When controlled for the potential confounding effects of school, year and season, multivariate negative binomial regression revealed a positive association between the level of appendicitis activity and the recorded rate of mumps (β=0·15, 95% CI 0·07–0·24, P<0·001). Non-significant associations were identified between appendicitis and the other sample infectious diseases. Subject to data caveats, our findings suggest that further studies are required to determine whether the comorbid association between mumps and appendicitis is causal.