Different schedules for pediatric use of the 13-valent pneumococcal conjugate vaccine (PCV-13) are recommended in different countries and the U.S. Advisory Committee on Immunization Practices (ACIP) has considered potential of changing from 3 primary doses plus a booster (3p + 1) to two primary doses plus a booster (2p + 1) for protection against Streptococcus pneumoniae. In this paper, we report results of IgG antibody measured by ELISA and opsonophagocytic assay (OPA) after 2p, 3p, at child age 15 months of pre-booster and 18 months (post-booster) in serum samples opportunistically available from a prior study that focused on PCV effectiveness against AOM. A total of ~ 100 sera for each of the 4 study time points (390 sera tested) from 169 children were tested. Geometric mean concentrations (GMCs) and percentage of children exceeding the presumed protective antibody thresholds measured by ELISA and OPA were calculated. 2p doses produced lower antibody levels measured by ELISA but not OPA until the booster dose for serotypes 6A, 6B, 5 and 23F only. Booster dosing at 15 months resulted in significant increases in antibody. There was no difference in the percentage of children with ≥ correlate of protection (COP) for OPA for 2p vs 3p doses except for serotype 23F. A 2p + 0 or 3p + 0 schedule would likely result in many children failing to sustain protective levels of antibody into the second year of life. We conclude that protection from invasive pneumococcal infection in early childhood would be similar for most serotypes in PCV13 using a 2p + 1 or 3p + 1 but not a 2p + 0 or 3p + 0 schedule.