Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.