Background: The impact of multiple tracheal intubation (TI) attempts on outcomes in critically ill children with acute respiratory failure is not known. The objective of our study is to determine the association between number of TI attempts and severe desaturation (SpO2 < 70%) and adverse TI associated events (TIAEs). Methods: We performed an analysis of a prospective multicenter TI database (National Emergency Airway Registry for Children: NEAR4KIDS). Primary exposure variable was number of TI attempts trichotomized as one, two, or ≥3 attempts. Estimates were adjusted for history of difficult airway, upper airway obstruction, and age. We included all children with initial TI performed with direct laryngoscopy for acute respiratory failure between 7/2010-3/2013. Our main outcome measures were desaturation (<80% during TI attempt), severe desaturation (<70%), adverse and severe TIAEs (e.g., cardiac arrest, hypotension requiring treatment). Results: Of 3382 TIs, 2080(65%) were for acute respiratory failure. First attempt success was achieved in 1256/2080(60%), second attempt in 503/2080(24%), and ≥3 attempts in 321/2080(15%). Higher number of attempts was associated with younger age, history of difficult airway, signs of upper airway obstruction, and first provider training level. The proportion of TIs with desaturation increased with increasing number of attempts (1 attempt:16%, 2 attempts:36%, ≥3 attempts:56%, p < 0.001; adjusted OR for 2 attempts: 2.9[95% CI:2.3-3.7]; ≥3 attempts: 6.5[95% CI: 5.0-8.5], adjusted for patient factors). Proportion of TIs with severe desaturation also increased with increasing number of attempts (1 attempt:12%, 2 attempts:30%, ≥3 attempts:44%, p < 0.001); adjusted OR for 2 attempts: 3.1[95% CI:2.4-4.0]; ≥3 attempts: 5.7[95% CI: 4.3-7.5] ). TIAE rates increased from 10 to 29to 38% with increasing number of attempts (p < 0.001); adjusted OR for 2 attempts: 3.7[95% CI:2.9-4.9] ≥3 attempts: 5.5[95% CI: 4.1-7.4]. Severe TIAE rates went from 5 to 8 to 9% (p = 0.008); adjusted OR for 2 attempts: 1.6 [95% CI:1.1-2.4]; ≥3 attempts: 1.8[95% CI:1.1-2.8]. Conclusions: Number of TI attempts was associated with desaturations and increased occurrence of TIAEs in critically ill children with acute respiratory failure. Thoughtful attention to initial provider as well as optimal setting/preparation is important to maximize the chance for first attempt success and to avoid desaturation.