Objective: To evaluate the safety of fentanyl in non-intubated infants undergoing peripherally inserted central catheter (PICC) placement. Methods: A retrospective chart review of PICC placements over a 3 years' period. We compared the 12h periods before and after fentanyl for clinically significant cardiorespiratory events (spells). Results: Of the 998 neonates screened, 258 were eligible. The mean standard deviation gestational age was 34.1 (4.3) weeks and the median (inter-quartile range) postnatal age was 4 (7, 11) days. The mean (standard deviation) fentanyl dose was 0.6 (0.2) μg/kg. Respiratory depression occurred only in two infants (prevalence rate = 0.78%, 95% CI (0, 1.85)). No cases of hypotension or chest wall rigidity occurred. There was no evidence of an increase in the number of infants with spells or in the number of spells per infant (p = 0.34 and p = 0.06, respectively). Conclusion: Fentanyl appears to be associated with only a small risk of respiratory depression in non-intubated infants.