Combination therapy with anticholinergics and β2-agonists should be used in COPD patients after failure of previous monotherapy with one of these drugs. Synergistic effect of both mechanisms of bronchodilation can maximize the efficacy of separately administered drugs. The effectiveness of the combination of LABA and LAMA is already confirmed, nevertheless the question about the safety profile of this therapy is still remaining, particularly with regard to the cardiovascular system. The paper discusses the overall safety profile of the combined preparation compare to placebo as well as the active comparators, especially the cardiovascular safety of fixed-dose formulation. Based on the data it has been demonstrated, that the combination of two ultra -long-acting bronchodilators with different complementary mechanisms of action increases the effectiveness of COPD therapy without affecting the safety.