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Abstract Objective: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. Methods: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn’s age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child’s age at diagnosis of disease. Results: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3–7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th–75th) of 9.0 (7.0–13.0) days. Conclusions: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve. Objective (CF NBS (NBS Methods populationbased population IRT/IRT. IRTIRT /IRT. (IRT)/IRT registry search newborns s laboratory childs child disease Results 826 82 6 82.6 1017576 1 017 576 1,017,57 occurred fiveyear year 120,767 120767 20,767 20 767 1:20,76 25th75th thth 25th 75th th (25th-75th 35 3 5 3. 2.3–7.3 2373 2 (2.3–7.3 months (IRT1 201 422 42 42. 483 48 48.3% 236 23 23.6 199 19 9 19.9 infants respectively followup. followup follow up. up 25th–75th (25th–75th 90 0 9. 7.0–13.0 70130 13 (7.0–13.0 Conclusions CFNBS progressively However problems improve IRT/IRT /IRT 8 82. 101757 01 57 1,017,5 120 120,76 12076 20767 20,76 76 1:20,7 2.3–7. 237 (2.3–7. (IRT 4 48.3 23. 19. 7.0–13. 7013 (7.0–13. 10175 1,017, 12 120,7 1207 2076 20,7 1:20, 2.3–7 (2.3–7 48. 7.0–13 701 (7.0–13 1017 1,017 120, 207 20, 1:20 2.3– (2.3– 7.0–1 70 (7.0–1 101 1,01 1:2 2.3 (2.3 7.0– (7.0– 10 1,0 1: 2. (2. 7.0 (7.0 1, (2 7. (7. ( (7