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Pneumococcal conjugate vaccine (PCV) immunization of children decreases their risk of nasopharyngeal acquisition of vaccine serotypes. We studied the impact of routine infant PCV immunization alone on the epidemiology of nasopharyngeal pneumococcal colonization among a rural African community with high prevalence of HIV positivity.Two cross-sectional surveys were undertaken in a rural South African community from May to October 2009 (period 1) and 2011 (period 2). Seven-valent PCV was introduced into the public immunization program for infants in April 2009, without catch-up campaign for older children. Randomly selected households with at least 1 child <2 years of age were recruited. Nasopharyngeal swabs from all consenting household members were obtained for Streptococcus pneumoniae culture and serotyping by Quellung method.The median ages (SD) of children enrolled were 4.32 (SD, 3.4) and 3.80 (SD, 3.4) years in periods 1 and 2, respectively. Overall, the prevalence of vaccine serotype colonization declined from 18.3% (368/2010) in period 1 to 11.4% (418/3659) by period 2 (P < 0.0001). This included reductions (adjusted risk ratio) of 50% [95% confidence interval (95% CI): 0.42–0.59], 34% (95% CI: 0.48–0.92) and 64% (95% CI: 0.18–0.74) in age groups <2 years, 6–12 years and adults. The prevalence of vaccine serotype colonization among primary caregivers decreased from 10.2% to 5.4% (P ≤ 0.001) by period 2. The prevalence of nonvaccine serotype colonization increased by 35% (95% CI: 1.17–1.56) among <2-year-old children by period 2, while it declined by 45–54% among adolescents and adults.An indirect effect of PCV7 was realized in a high HIV prevalence setting within 2 years of PCV introduction. The unexpected decline in nonvaccine serotypes colonization among adolescents/adults may indicate lag in replacement colonization by nonvaccine serotypes in this group.