The hexavalent vaccine Infanrix hexa was introduced into the national childhood vaccination schedule in the Netherlands in 2006. It is offered, concomitantly with pneumococcal vaccine (Prevenar), to children at increased risk of hepatitis B, administered in a 4-dose schedule at 2, 3, 4 and 11 months of age. We assessed the immunogenicity of the HBV component of Infanrix hexa co-administered with Prevenar, and compared pertussis and Hib components in Infanrix hexa with the standard Infanrix-IPV+Hib vaccine. Target thresholds for immune responses were achieved for all antigens studied. Over 99% (163/164) of children vaccinated with Infanrix hexa achieved an adequate immune response (≥ 10 mIU/ml) to the HBV component and peak anti-HBs geometric mean concentration (GMC) was 2264 mIU/ml (95%CI:1850-2771 mIU/ml). The GMC of a pertussis component, filamentous hemagglutinin (FHA), of Infanrix-hexa was significantly lower in children vaccinated with Infanrix hexa and Prevenar than in children vaccinated with Infanrix-IPV+Hib. Universal infant HBV vaccination using Infanrix hexa was introduced in The Netherlands in 2011. Despite very high rates of seroconversion for the HBV component of Infanrix hexa, its long term immunogenicity and effectiveness should be monitored after concomitant vaccination.