- Background The 7-valent pneumococcal conjugate vaccine (PCV7) was initially licensed for use as 3 infant doses and a booster (3 + 1). However, 2 infant doses plus a booster schedules only (2 + 1) are widely used. We compared the effect of these two schedules on pneumococcal carriage in young children. We also assessed the effect of a 2-dose schedule in the second year (“catch-up” schedule; 0 + 2). Methods Subjects ( n = 733) were randomized to the 2 + 1 (4, 6, 12 m), 3 + 1 (2, 4, 6, 12 m) or 0 + 2 (12, 18 m) schedules. Blood samples for serotype-specific IgG (SSIgG) determination were obtained at 2, 7, 13, 19 months, and nasopharyngeal + oropharyngeal pneumococcal cultures were obtained at 2, 4, 6, 7, 12, 13, 18, 19, 24, 30 months. Results After primary infant PCV7 series, SSIgG was significantly lower for four out of seven serotypes in children receiving 2 doses compared to 3 doses, particularly for serotypes 6B and 23F. This was associated with a higher acquisition and prevalence rates of vaccine serotype carriage in the 2-dose group, particularly serotypes 6A and 6B. After the booster dose at 12 months of age, most differences were not significant anymore. A single PCV7 dose at age 12 months in previously unvaccinated subjects (“catch up” schedule) resulted in poor SSIgG concentrations for three out of seven serotypes, resulting in higher acquisition and prevalence rates of vaccine serotypes (grouped) compared to infants receiving a booster dose at 12 months (2 + 1 and 3 + 1 groups). Similarly, serotypes 6B and 6A also showed significantly higher carriage rates after a single dose at 12 months. After the second catch-up dose at 18 months, the rates were similar to those in the 2 + 1 or 3 + 1 schedules, except for serotype 6A. Conclusions Three infant doses seem to better protect against PCV7-serotype acquisition and carriage than two. However, after booster, most of these differences disappear. A 2-dose second year catch-up campaign may enhance the reduction of PCV7-serotype spread in the community.