Background: Bronchial anthracosis is the black discoloration of bronchial mucosa that exhibits similar manifestations to Chronic Obstructive Pulmonary Disease ( COPD). The etiology of this obstructive lung disease has not been elucidated and standard therapy for this disease has not been introduced in the literature. The objective of this study is to determine the efficacy of the salmeterol-fluticasone inhaler and tiotropium as two safe treatments of obstructive lung disease for the treatment of symptomatic subjects of anthracofibrosis of the lung. Materials and Methods: Twenty anthracofibrosis subjects who suffered from dyspnea were enrolled in this three-phase, cross over, placebo-controlled clinical trial. The primary outcome variable was quality of life (evaluated with the CAT questionnaire). Clinical findings and spirometry were the secondary outcome variables. Both of these drugs were delivered by an inhaler and were made identically by the reference manufacturer. Salmeterol-fluticasone was prescribed with a spacer and tiotropium by its special device, and the method of utilization was taught to the patients. Results: Twenty anthracofibrosis subjects were enrolled in this three-phase, five-month course of treatment with either salmeterol-fluticasone or tiotropium inhalers. The response to therapy was not good; neither for salmeterol-fluticasone nor for tiotropium in the short course of the treatment. However, the overall results of 5 months of therapy with both of the drugs have shown improvement in 57% of the subjects. The most prominent results were found in the CAT score [25.1±5.54 before the trial, which decreased to 19.2±5.14 (Z score=2.7, P=0.007)] and clinical findings especially sputum, chest pain, and wheezing (81, 94 and 92% before the trial and 50, 56, 54% after the trial, respectively). Neither clinical findings nor spirometry was able to predict a good response to salmeterol-fluticasone or tiotropium. Conclusion: The combination of salmeterol-fluticasone and tiotropium inhaler was able to improve the clinical findings of symptomatic anthracofibrosis patients.