Introduction: The long-acting anticholinergic Tiotropium, which used in the treatment of patients with chronic obstructive pulmonary disease, prescribed once a day, unlike other bronchodilators that used several times a day for patients. The study was a systematic review that examined the effectiveness and safety of b2 Agonists and Tiotropium in the patients with chronic obstructive pulmonary disease.Methods: RCT (randomized controlled trials) and CCT (controlled clinical trials) studies that compared Tiotropium and b2 agonists extracted from PubMed, SCOPUS, Ovid Medline and Cochran databases regardless of the time limitation were studied. Only studies were reviewed that were in English. In total, eight articles have been evaluated. Meta-analysis was performed using STATA software Conclusions: The results showed less efficacy based on two outcomes include FEV1 (Forced expiratory volume in 1 second) and FEV1 / FVC, and a little higher efficacy based on other outcomes such as (FVC). In terms of safety it can be said, the overall incidence of adverse events in both treatments was the same and it has been reported from moderate to severe according to the findings. Mostly, serious side effects were in form of intensifying attacks. The percentage of patients with severe complications in the Tiotropium group were less than Salmeterol group (0.9 vs.3.1%, p=0.04). In addition, a limited number of deaths observed in both treatment which were often unrelated to the applied treatment.Conclusion: The results showed that Tiotropium treatment compared to β2 agonists was superior to safety. On the other hand, it showed less efficacy in the efficacy outcomes (FEV1 and FEV1 / FVC), and in the case of (FVC) effectiveness at a higher rate.