The aim of this study was to determine whether there is a relationship between appendectomy and pulmonary tuberculosis in Taiwan. We designed a case-control study by analyzing the database from the Taiwan National Health Insurance Program. In total, we found 11,366 individuals (aged 20 years and older) with newly diagnosed pulmonary tuberculosis as the case group and 45,464 individuals without pulmonary tuberculosis as the control group from 1998 to 2011. The case group and the control group were matched on sex, age, and index year of diagnosing pulmonary tuberculosis. Using the multivariable unconditional logistic regression model, we measured the odds ratio (OR) and 95 % confidence interval (CI) for the risk of pulmonary tuberculosis associated with appendectomy and other comorbidities. After controlling for covariables, the multivariable unconditional logistic regression model disclosed that the OR of pulmonary tuberculosis was 1.4 in appendectomized patients (95 % CI = 1.13, 1.75) when compared to individuals without appendectomy. In further analysis, comorbidity with chronic obstructive pulmonary diseases (OR = 4.63, 95 % CI = 3.21, 6.68), pneumoconiosis (OR = 7.80, 95 % CI = 1.43, 42.5), chronic kidney diseases (OR = 5.65, 95 % CI = 1.79, 17.8), or diabetes mellitus (OR = 2.11, 95 % CI = 1.30, 3.44) increased the risk of pulmonary tuberculosis in appendectomized patients. Individuals with appendectomy are at a 1.4-fold increased risk of pulmonary tuberculosis. Comorbidities, including chronic obstructive pulmonary disease, pneumoconiosis, chronic kidney diseases, and diabetes mellitus, enhance the risk of pulmonary tuberculosis.