Level of Evidence: 3 Objective(s) To identify the risk factors for Cholesteatoma in a large UK cohort. Although some risk factors are well established (male sex, history of chronic otitis media), others require further evidence (deprivation, smoking). Design and Setting 1,140 cholesteatoma cases from UK BioBank were compared to 4,551 non-cholesteatoma middle ear disease and 493,832 ear disease-free controls. Adjusted odds ratios were calculated for demographic factors including age, sex, ethnicity, deprivation and smoking status with logistic regressions. Odds ratios for overlapping ICD-10 codes are also calculated. Results Cholesteatoma was significantly associated with sex (Adjusted odds ratio (AOR) for males=1.33), age (AOR=1.02) and deprivation (AOR=1.08) compared to ear disease-free controls ( p<0.001). Age and deprivation distributions for cholesteatoma and non-cholesteatoma ear disease were similar. Although there was no significant association with smoking status, cholesteatoma was significantly associated with the ICD-10 code mental and behavioural disorders due to tobacco use (OR=2.34, p<0.001). Cholesteatoma was also strongly associated with a wide range of inflammatory middle ear conditions and chronic sinus inflammation, suggesting an increased susceptibility to inflammation of the upper airways. Conclusion This study shows a large overlap between cholesteatoma and non-cholesteatoma ear disease in terms of numbers and demographics, with sex being a key factor distinguishing between the two, suggesting that there are both common and distinct risk factors exist.