Lack of paternal involvement has been shown to be associated with adverse pregnancy outcomes, including infant morbidity and mortality, but the impact on health care costs is unknown. Various methodological approaches have been used in cost minimization and cost effectiveness analyses and it remains unclear how cost estimates vary according to the analytic strategy adopted. We illustrate a methodological comparison of decision analysis modeling and generalized linear modeling (GLM) techniques using a case study that assesses the cost-effectiveness of potential father involvement interventions. We conducted a 12-year retrospective cohort study using a statewide enhanced maternal-infant database that contains both clinical and nonclinical information. A missing name for the father on the infant’s birth certificate was used as a proxy for lack of paternal involvement, the main exposure of this study. Using decision analysis modeling and GLM, we compared all infant inpatient hospitalization costs over the first year of life. Costs were calculated from hospital charges using department-level cost-to-charge ratios and were adjusted for inflation. In our cohort of 2,243,891 infants, 9.2 % had a father uninvolved during pregnancy. Lack of paternal involvement was associated with higher rates of preterm birth, small-for-gestational age, and infant morbidity and mortality. Both analytic approaches estimate significantly higher per-infant costs for father uninvolved pregnancies (decision analysis model: $1,827, GLM: $1,139). This paper provides sufficient evidence that healthcare costs could be significantly reduced through enhanced father involvement during pregnancy, and buttresses the call for a national program to involve fathers in antenatal care.