Background: Noninvasive positive-pressure ventilation (NIPPV) has been safely used in selected patient populations. The purpose of this study was to determine the safety and efficacy of NIPPV outside the intensive care unit (ICU) in a tertiary hospital. This descriptive, cross sectional study was performed at Masih Daneshvari Hospital, Tehran, Iran during 2011 - 2015. Methods: Between March 2011 and June 2015, patients requiring NIPPV were enrolled in the study. The study population included all eligible patients. Census sampling was applied in this study. The patients’ medical history (including comorbidities), age, sex, and hospital ward in which NIPPV was delivered were assessed retrospectively. Moreover, venous pH, partial pressure of carbon dioxide (PCO2), and bicarbonate (HCO3-) were analyzed before and after the intervention (NIPPV application). Results: A total of 946 patients, including 598 (63.2%) men and 348 (36.8%) women, received NIPPV for inpatient hospital care. The mean age of the patients was 61.92 ± 15.5 years (range, 3 - 102 years). Indications for NIPPV included exacerbation of chronic obstructive pulmonary disease (COPD; 55.4%), obstructive sleep apnea (OSA; 6%), bronchiectasis (7.8%), concurrence of COPD and OSA (4.8%), neuromuscular disorders (1.7%), congestive heart failure (4%), postthoracotomy pain (0.6%), thoracic malignancy (2.1%), pulmonary thromboembolism (1.1%), pneumonia (7.3%), asthma (1.5%), interstitial lung disease (2.5%), tuberculosis (4%), and cystic fibrosis (1.3%). We found significant improvements in venous pH and PCO2 with no significant changes in HCO3- (P > 0.05). Conclusions: NIPPV could be safely used under the supervision of trained pulmonologists in non-ICU settings. This method was effective in treating acute abnormalities in venous blood gas, including pH and PCO2.