Objective: To evaluate whether the initial pressure level on High CPAP (≥9 cmH2O), in relation to pre-extubation mean airway pressure (Paw), influences short-term clinical outcomes in preterm neonates. Design/Methods: In this retrospective-cohort study, preterm neonates <29 weeks’ gestational age (GA) extubated from mean Paw ≥9 cmH2O and to High CPAP (≥9 cmH2O) were classified into “Higher-level CPAP” (2-3 cmH2O higher than pre-extubation Paw) and “Equivalent CPAP” (-1 to +1 cmH2O in relation to pre-extubation Paw). Only the first eligible extubation per infant was analyzed. The primary outcome was failure within ≤7 days of extubation, defined as any one or more of: (a) need for re-intubation, (b) escalation to an alternate non-invasive respiratory support mode, or (c) use of CPAP >pre-extubation Paw +3 cmH2O. Secondary outcomes included individual components of the primary outcome, along with other clinical and safety outcomes. Results: Over a 10 year period (Jan 2011 to Dec 2020), 175 infants were extubated from mean Paw >9 cmH2O to High CPAP pressures. Twenty-seven subjects [median (IQR) GA 24.7 (24.0-26.4) weeks and chronological age 31 (21-40) days] were classified into the “Higher-level CPAP” group while 148 infants [median (IQR) GA 25.4 (24.6-26.6) weeks and chronological age 26 (10-39) days] comprised the “Equivalent CPAP” group. There was no difference in the primary outcome (44% vs. 51%; P=0.51), including post-adjustment for confounders (adjusted OR 0.47 [95% CI 0.17-1.29; P=0.14]). However, re-intubation risk within 7 days was lower with Higher-level CPAP (7% vs. 37%; P<0.01), including post-adjustment (aOR 0.07; 95% CI 0.02-0.35; P<0.01). Conclusions: In this cohort, use of initial distending CPAP pressures 2-3 cmH2O higher than pre-extubation Paw did not alter the primary outcome of failure, but did lower the risk of re-intubation. The latter is an interesting hypothesis-generating finding that requires further confirmation.