Background and Purpose: Population study on relationship between nontuberculous mycobacterial (NTM) infection and respiratory failure (RF) is limited. This study evaluated the RF risk, including acute respiratory failure (ARF), chronic respiratory failure (CRF) and ARF on CRF, in patients with NTM infection in Taiwan. Methods: We used the National Health Insurance Research Database of Taiwan to identify 3864 newly diagnosed NTM patients (NTM cohort) from 1999 to 2009, and 15456 non-NTM patients (non-NTM cohort), frequency matched by demographic status for comparison. Incidence and hazard of developing RF were measured by the end of 2010. Results: The incidence rate of RF was 4.31-fold higher in the NTM cohort than in the non-NTM cohort (44.0 vs. 10.2 per 1000 person-years), with an adjusted hazard ratio (HR) of 3.11 (95% CI: 2.73-3.54). The cumulative proportional incidence of RF was 10% higher in the NTM cohort than in the non-NTM cohort (P<0.0001). The RF risk was much greater within 6 months after the diagnosis of NTM infection with a HR of 7.45 (95% CI = 5.50-10.09). Age-specific comparison showed that the younger NTM patients had a higher HR of RF than the elderly NTM patients (HR: 4.42, 95% CI: 3.28-5.96 vs. HR: 2.52, 95% CI: 2.17-2.92). Comorbidity increased the risk of RF in both cohorts, particularly in those with chronic obstructive pulmonary disease. Conclusion: Our study suggests patients with NTM infection are at a high risk of RF. The risk appears much greater soon after patients diagnosed with NTM infection.