Streptococcus pneumoniae is a primary cause of illness and death among children younger than 5 years in China. The heptavalent pneumococcal conjugate vaccine (PCV7) was the only conjugated vaccine (PCV) available in China from 2008 to 2013. This randomized, controlled, open-label study conducted at 46 Beijing clinics involved 3281 healthy 2-5-year-old Chinese children, randomized 1:1 to receive one dose of the S. pneumoniae heptavalent conjugated vaccine (PCV7) (n = 1643) or Haemophilus influenzae type b conjugate vaccine (Hib) (n = 1638). The main objective of this study was to investigate the impact of PCV7 against that of Hib vaccination in the nasopharyngeal S. pneumoniae colonization in healthy Chinese children. Nasopharyngeal (NP) samples for culture, serotyping and antimicrobial susceptibility testing were collected before vaccination and at Day 60 and 180 post-vaccination. A total 3281 children were enrolled in the study. Demographic characteristics were similar among both study groups: 1641 children received PCV7. Before immunization, S. pneumoniae was isolated in 338 and 360 children in the PCV7 (144 PCV7 isolates) and Hib groups (145 PCV7 isolates), respectively. At Day 180, PCV7 vaccination was more effective than Hib vaccination in reduction NP carriage (20.2% [P = 0.052]) and new acquisition (19.0% [P = 0.066]). When reductions in NP carriage and new acquisition of PCV7 VT plus 6A was analyzed, reduction in the PCV7 vaccinated group achieved statistical significance (P = 0.034 and P = 0.042 versus Hib, respectively). NP carriage of NVT increased in both groups (P = 0.305 between study groups at Day 180). PCV7 decreased NP carriage of non-susceptible VT to amoxicillin (P = 0.000), ceftriaxone (P = 0.047) and MDR (P = 0.024) versus Hib. PCV7 vaccination in Chinese children 2 to 5 years of age was more effective than vaccination with Hib in the reduction of S. pneumoniae nasopharyngeal carriage, new acquisition and non-susceptible isolates.