There is presently no licensed oral form of vitamin K1 for prophylactic use in neonates in the USA. The purpose of this study was to compare a new oral preparation of vitamin K1 (Konakion MM™) containing lecithin and glycocholic acid with a standard intramuscular (IM) preparation during the first 8 weeks of life. All infants were born at term at two hospitals in the USA and exclusively breastfed during the study. With randomization occurring at the time of birth, 79 infants received oral vitamin K (three doses[2 mg] at birth, 7 and 30 days of life) and 77 received a single IM dose (1 mg) at birth. 67 infants in each group completed 8 weeks of the study. Prothrombin time (PT) and vitamin K1 (adult normal 0.66, range 0.15-1.55 ng/ml) were monitored at 14, 30, and 56 days.. PIVKA-II (des-gamma-carboxyprothrombin elevated in vitamin K deficiency) levels was measured at birth (cord blood), 14, 30, and 56 days of life. Following newborn prophylaxis, vitamin K1 concentrations showed a decline in both groups over time but stabilized in the oral group by 30 days. Vitamin K1 (ng/ml ± SD) remained higher in the oral group at 14 & 56 days: 2.0±1.6 vs 1.3±1.1 (p<0.007), 0.5±0.3 vs 0.5±0.7 (p<0.11), 0.5±0.8 vs 0.2±0.2(p< 0.0003) at 14,30,&56 days respectively. PIVKA-II was detectable(≥ 0.1 AU/ml) in cord blood in 47% of the infants. By 14 days, only one infant in each group had a detectable PIVKA-II (0.4 AU/ml IM group, 0.1 AU/ml oral group), both of whom had high levels of PIVKA-II in cord blood. At 30 days, there were no detectable PIVKA-II's in either group. At 56 days, there were no detectable PIVKA-II's in the oral group; however three infants in the IM group had positive values of 0.1, 0.2, & 1.09 AU/ml. Respective plasma vitamin K's in these infants were 0.15, 0.1 & < 0.05 ng/ml. Prothrombin times were not elevated. We conclude: 1) Plasma vit K1 concentrations were at least equal to and/or higher after the new oral vit K1 regimen compared to the IM regimen at the time points measured, 2) Through 8 weeks of life, the new oral preparation maintains hemostasis and plasma vit K in breast fed infants.