ABSTRACT Background Due to the dysfunction and destruction of pancreatic cells in individuals with cystic fibrosis (CF), most require lifelong exogenous pancreatic enzyme supplementation. The objective of this study was to determine if elexacaftor/tezacaftor/ivacaftor (ETI) treatment improves pancreatic function in individuals with CF. Methods A retrospective study was conducted utilizing CF Foundation Patient Registry data for individuals 0–21 years receiving care at the Tulsa CF Center. Data collected included demographic variables, fecal elastase (FE‐1) values, BMI percentile, and CFTR mutations. Pancreatic sufficiency was defined as “severe” (< 100), “moderate” (100–200), and “sufficient” (> 200). Descriptive statistics, and Spearman Correlation post‐hoc analysis ( p < 0.05) were performed. Results The majority of individuals with a post‐ETI FE‐1 value ( n = 49) were homozygous for the F508del mutation ( n = 38, 78%). After ETI, most individuals had severe pancreatic insufficiency ( n = 39, 79.6%) followed by 10.2% ( n = 5) with moderate insufficiency and 10.2% ( n = 5) with sufficiency. The median time between ETI initiation and highest post‐FE‐1 ranged from 14.07 months (IQR: 8.78–14.07) for the pancreatic sufficient group to 18.87 months (IQR: 10.42‐33.04) for the severe pancreatic insufficiency group. The five individuals achieving post‐ETI sufficiency had a mean time of 10.95 months (SD = 6.18) between start of therapy and conversion to pancreatic sufficiency. Age at ETI start and FE‐1 value were moderately negatively correlated ( p = 0.0024) with pancreatic sufficient individuals having the youngest median initiation age (5.28 years, IQR: 2.95–5.54). All pancreatic sufficient individuals at the post‐ETI assessment had homozygous F508del CFTR mutations ( n = 5). Twenty‐four individuals had both pre‐and‐post‐ETI FE‐1 values. Of those 24, two converted (8.3%) to moderate sufficiency, and three (12.5%) to pancreatic sufficient. Conclusion While exploring the impacts of ETI therapy on pancreatic function, this study revealed a potential reversal of pancreatic insufficiency. The results suggest the importance of early initiation of therapy and standardized protocols to monitor FE‐1 values over time.