Background: Microscopic smear examination is the most common test in tuberculosis (TB) detection. It is, however, not strong enough to identify TB in the majority of afflicted individuals; thus, a significant number of TB patients are smear negative and capable of transmitting the infection. The aim of this study was to evaluate the rate of smear-negative TB in northwest Iran.Methods: In this cross-sectional study, 329 TB-confirmed patients were evaluated through culture up to March 1, 2015, in northwest Iran. The demographic and clinical features of the smear-negative and smear-positive TB patients were compared. The χ2 test was used to compare the frequency of the variables. All the statistical analyses were conducted using SPSS, version 16 (Chicago, IL, USA).Results: Seventy-five cases were smear negative and 254 were smear positive. Smokers, asthmatics, and extra-pulmonary TB patients were primarily among the smear-negative cases. The rate of mortality was also relatively higher among the smear-negative TB patients.Conclusion: Totally, 22.8% of the TB cases in northwest Iran were smear negative, with a relatively higher rate of mortality than those with positive smears. A delay in these patients’ return to TB diagnosis and treatment centers increases the chance of transmission to others. This is a very sensitive issue in centers where there is no equipment for TB cultivation. Thus, it is essential to equip centers without TB cultivation facilities and to use appropriate diagnostic techniques in centers with those facilities to help rapidly detect smear-negative cases.