Objective To analyze the key points of differential diagnosis between stage Ⅲ pneumoconiosis and secondary tuberculosis with large nodular shadow using high-resolution CT (HRCT) in the elderly with a view to improving the diagnostic accuracy of stage Ⅲ pneumoconiosis in the elderly. Methods A retrospective analysis was made of 43 cases of stage Ⅲ pneumoconiosis and 55 cases of secondary tuberculosis with large nodular shadow in the elderly. The two groups were compared in their general information and imaging characteristics. Statistical analysis was performed using SPSS statistics 22.0. Results As for clinical manifestations, there were significant differences between the two groups in five factors:gender, hemoptysis, chest pain, wheeze, and dyspnea(P＜0.05). As for CT features, there were significant differences between the two groups in 10 factors:bilateral upper lobes, upper left lobe, calcification in the big shadow, cavity, emphysema around the big shadow, miliary shadow in the lung, bronchiectasis, hilar lymph node enlargement,hilar lymph node calcification and calcification of mediastinal lymph nodes(P＜0.05). Conclusions HRCT shows specificity of some degree for stage Ⅲ pneumoconiosis in the elderly, which can improve the diagnostic accuracy if combined with the clinical manifestations.