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RATIONALE The endotracheal tube (ETT) is the most common route for invasive mechanical ventilation (MV) yet controversy attends its long-term safety. OBJECTIVE Assess the safety of ETT compared with tracheostomy tube (TT) for MV support in the intensive care unit (ICU). METHODS Retrospective analysis of five year national dataset of 128,977 adults (age > 15-years) admitted for MV therapy with tracheostomy tube (TT; n = 4772) or without (ETT; n = 124,204), excluding those with neurological diagnoses or likely to require a surgical airway (n = 27,466), in 93 public health service ICUs across Australia, between July 2013-June 2018. MEASUREMENTS Hospital survival (including liberation from MV) for ETT Group compared with TT Group using a probit regression model adjusted for confounding using fixed, endogenous and non-random treatment assignment covariates, and their interactions; analysed and plotted as marginal effects by duration of MV. RESULTS Median duration of MV was 2 (IQR =1-4) days, predominantly via ETT (124,205; 96.3%), and 21,620 (16.7%) died. Temporal trend for ETT increased (OR = 1.06 per year, 95%CI =1.03-1.10) compared to TT, even for prolonged (>3 weeks) MV (38.1%). Higher risk-adjusted mortality was associated with longer duration of MV and after 9 days of MV with retention of ETT compared with TT - average (mortality) treatment effect 12.6% (95%CI =10.7-14.5). The latter was not significant after 30 days of MV. CONCLUSIONS The safety of ETT compared with TT beyond short-term MV (≤9-days) is uncertain and requires prospective evaluation with additional data.