BACKGROUND AND OBJECTIVE: Refusal of intramuscular (IM) vitamin K administration by parents is an emerging problem. Our objective was to assess the frequency of and factors associated with refusal of IM vitamin K administration in well newborns in the United States. METHODS: We determined the number of newborns admitted to well newborn units whose parents refused IM vitamin K administration in the Better Outcomes through Research for Newborns network and, in a nested patient-control study, identified factors associated with refusal of IM vitamin K administration by using a multiple logistic regression model. RESULTS: Of 102 878 newborns from 35 Better Outcomes through Research for Newborns sites, parents of 638 (0.6%) refused IM vitamin K administration. Frequency of refusal at individual sites varied from 0% to 2.3%. Exclusive breastfeeding (adjusted odds ratio [aOR] = 3.4; 95% confidence interval [CI]: 2.1–5.5), non-Hispanic white race and/or ethnicity (aOR = 1.7; 95% CI: 1.2–2.4), female sex (aOR = 1.6; 95% CI: 1.2–2.3), gestational age (aOR = 1.2; 95% CI: 1.1–1.4), and mother’s age (aOR = 1.05; 95% CI: 1.02–1.08) were significantly associated with refusal of IM vitamin K administration. Refusal of the administration of both ocular prophylaxis and hepatitis B vaccine was also strongly associated with refusal of IM vitamin K administration (aOR = 88.7; 95% CI: 50.4–151.9). CONCLUSIONS: Refusal of IM vitamin K by parents of newborns is a significant problem. Interventions to minimize risks to these newborns are needed.