Background For a few decades, non-invasive ventilation (NIV) has been regarded as an effective method in avoiding the use of endotracheal intubation (ETI) and decreasing mortality in patients with acute hypercapnic respiratory failure (AHRF). Recent evidence supports the suggestion that the inclusion of NIV into conventional intervention strategy may enhance outcomes in both patients with chronic obstructive pulmonary disease (COPD) exacerbation and those with acute cardiogenic pulmonary oedema (1). However, the effectiveness of NIV in patients with acute conditions after operations and in trauma is still questioned. A meta-analysis in 2015 suggested that the use of NIV as an adjunctive therapy in non-COPD and non-traumatic AHRF patients decreases the need for ETI, ICU length of stay, and mortality rate to significant levels (2). However, they concluded that the heterogeneity of the cohorts in the studies did not allow for definitive recommendations and further studies were required. Home mechanical ventilation (HMV) in the form of NIV is also an increasingly common intervention and is initiated for a range of pathological processes, including neuromuscular disease (NMD), chronic obstructive pulmonary disease (COPD) and obesity-related respiratory failure (3). Physiologic studies have shown that mechanical ventilation can improve alveolar ventilation while reducing inspiratory effort in patients with stable chronic hypercapnic respiratory failure (4). A number of potential mechanisms have been proposed to explain the beneficial effects of NIV in hypercapnic patients with COPD, including an increase in the central responsiveness to CO2, which is associated with improved daytime blood gases, changes in lung mechanics, improvement in ventilation/perfusion (V/Q) matching, recruitment of non-ventilated or poorly-ventilated alveolar units, and decreased pulmonary hypertension (5). Nevertheless, for over twenty years, the mentioned issues provoke many controversies. Aim and Hypothesis The study will answer the following question: can NIV implementation in patients with non-COPD be considered effective and what factors will define its efficacy? The formulated hypothesis is as follows: the application of NIV in the adjunctive treatment of non-COPD patients will help to reduce the need for ETI, the length of stay at intensive care unit, and the overall mortality rates. However, it is suggested that, in order to ensure a high level of NIV efficiency, the personnel should set up the ventilation parameters considering the distinctive properties of NIV which include oxygen leakages and additional variable resistance of the upper respiratory tract (6). Thus, the research also aims to determine what NIV regimes and intervention factors will be associated with greater efficiency and better patient outcomes in the treatment of non-COPD. Methods The research project will be carried out in three phases: The systematic review and meta-analysis of evidence on the use of NIV in acute and postoperative care for non-COPD respiratory failure and postoperatively. The given methodology is selected because the findings of systematic reviews are frequently far more valuable than the results of a separate study mainly due to the larger size of the sample (7). The data collected from about 200 scholarly and professional sources will be examined at this stage. Both qualitative and quan