BackgroundTuberculosis (TB) is a major cause of illness and death worldwide, especially in Asia and Africa. In the early 1990s tuberculosis control in Egypt faced many problems. Major progress in global tuberculosis control followed the widespread implementation of the DOTS strategy. AimThe objective of this work was to study the tuberculosis situation in Port Said governorate from (1995–2011) before and after Direct Observed Therapy Short Course Strategy (DOTS). MethodsThis was a retrospective clinical cohort study carried out at the Port Said governorate. The registered data about all TB cases over a period of 16years (1995–2011) before and after the application of DOTS were collected from the chest hospital and TB registration units. ResultsPercentages of cure and complete treatment significantly increased after DOTS (48.7% and 29.3% respectively) than before (19.5% and 13.7% respectively) (P<0.001). On the other hand, failure, death, default and transfer out decreased after DOTS (5.9%, 3.2%, 7.5% and 5.4% respectively) than before it (6.5%, 6.1%, 34.7% and 19.5% respectively), the results were significant (P<0.05) for all of them except treatment failure. The mean values of incidence rates (new and relapse cases, all cases and new smear positive pulmonary TB cases) of TB significantly (P<0.05) decreased after the application of DOTS. Also, the cure rate and treatment success rate significantly increased (P=0.001), while retreatment TB cases rate, default rate, transfer out rate and retreatment failure rate significantly decreased (P<0.05). Finally new pulmonary TB cases with no smear result significantly (P<0.05) increased after DOTS. ConclusionThe introduction of DOTS in the Port Said governorate has led to a significant increase in the treatment success (82.7%) (Near the WHO target “85%”), and a decrease in the default and failure rates.