Objective: To evaluate the safety and immunogenicity of two lots of a heptavalent Streptococcus pneumoniae conjugate vaccine (PCV) containing seven capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to the outer membrane complex of Neisseria meningitidis serogroup B (OMPC) and administered to infants at 2, 4, 6, and 12 months of age. Methods: One hundred twenty infants were randomly assigned to concurrently receive PCV-OMPC and one of two Haemophilus influenzae type b (Hib) conjugate-DTwP combination vaccines: (1) Hib with a heterologous protein carrier (CRM 197, TETRAMUNE ®, Group 1) or (2) an experimental Hib-hepatitis b combination vaccine with the homologous carrier (OMPC, Group 2). All infants in Groups 1 and 2 received PCV-OMPC (lot 1) at 12 months of age. Another separate group of 120 infants (Group 3) received a different lot of PCV-OMPC concurrently with Hib-CRM 197 (TETRAMUNE ®) at 2, 4, and 6 months of age and then were randomized to receive either PCV-OMPC or a 23-valent polysaccharide (PS) pneumococcal vaccine at 12 months of age. Results: Each PCV-OMPC lot was generally well tolerated and no vaccine-related serious adverse events were reported. Following the primary series, serotype-specific anti-pneumococcal geometric mean concentrations (GMC) were highest for serotypes 14, 19F, and 4 and lowest for serotypes 6B and 23F. GMC and seroconversion rates in Group 3 (lot 2) were lower than in Group 1 (lot 1) for serotypes 6B, 14, 18C, and 23F. Antibody responses to serotypes 6B, 14, and 18C were significantly lower in Group 2 compared to Group 1. Following a booster dose of PCV-OMPC at 12 months of age, each lot was immunogenic with at least a 5–10-fold increase in antibody levels, and responses were significantly higher among those who received the PS vaccine. Conclusions: PCV-OMPC is generally safe in infants, displays variable immune response by serotype, and concomitant receipt of Hib vaccine with homologous carrier may impact on its immunogenicity.