Background Tuberculosis (TB) is a major problem in developing countries. TB in Egypt is considered an important public health problem. Egypt is ranked among the mid-level incidence countries. Objective To evaluate TB status in 19 governorates and to compare the TB situation in Upper and Lower Egypt over 20 years from 1992 to 2012 before and after the application of directly observed treatment short-course strategy (DOTS). Patients and methods This is a retrospective study involving record review. The registered data were collected from TB registration units in the 19 governorates. Results The highest percentage of TB cases was in the age group 15-30 years. Infection was higher in males than females and in rural areas more than urban areas. Pulmonary TB and smear positivity at diagnosis, second, third, and fifth month were higher in Lower Egypt. Treatment after failure or relapse was significantly higher in Upper Egypt, whereas default rate, failure rate, and death rate were significantly higher in Lower Egypt. Regarding treatment outcome, cure, complete treatment, and transfer out were significantly increased after DOTS than before. Failure, default, and death were significantly reduced after DOTS than before DOTS. Upper Egypt included higher incidence rates of TB, new adult smear-positive cases, new extrapulmonary TB cases, and sputum conversion rate at the end of the initial phase of treatment. Cure rate and treatment success rate were significantly higher among patients of Upper Egypt, whereas transfer out rate and retreatment failure rate were significantly higher among Lower Egypt patients. Conclusion TB is still a health problem in Egypt, with pulmonary TB more in Lower Egypt, whereas extrapulmonary more in Upper Egypt, but after the introduction of DOTS, there is a significant increase in cure and success rate, with markers of success being more in Upper Egypt.