We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. The primary outcome was FEF at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF and FEF obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (  = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (  =  109) as measured by FEF (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval CI for difference, -3.33 to 35.64;  = 0.10), FEF (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30;  = 0.02), and FEF (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34;  = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Although the primary outcome of FEF was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF and FEF were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF and FEF ) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).