AIM:: To test for immunologic non-inferiority of antibody responses to Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared with DTPa-IPV-Hib plus MenC-CRM197, before and after a 12-month Hib-MenC-TT booster. METHODS:: Pragmatic open-label, randomized, multi-center, UK study. '6-in-1' group received DTPa-IPV/Hib-MenC-TT at 2, 3 and 4 months; control group received DTPa-IPV-Hib at 2, 3 and 4 months, and MenC-CRM197 at 3 and 4 months. Both groups received Hib-MenC-TT at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4 and 13 months, MMR vaccine at 13 months. RESULTS:: 142 children were randomized to each group. 100 children in the '6-in-1' group and 112 control group children completed the study according-to-protocol. One month post-primary immunizations: 100% of '6-in-1' group and 93.3 % of control children had anti-PRP IgG >0.15 µg/mL; 96.2% and 100% respectively had rSBA-MenC titers >1:8. One month post-booster all children met these thresholds, with anti-PRP GMCs of 66.7 [53.3; 83.5] in '6-in-1' recipients and 26.9 [20.9; 34.6] in control children (4.4 [3.5; 5.4] and 3.0 [2.2-4.2] post-primary immunizations, respectively,). rSBA-MenC GMTs were 3062.9 [2421.2; 3874.6] and 954.0 [761.3; 1195.5] respectively post-booster and 393.2 [292.5; 528.7] and 3110.5 [2612; 3704.2] post-primary. CONCLUSION:: Non-inferiority of DTPa-IPV/Hib-MenC-TT compared with DTPa-IPV/Hib plus MenC-CRM197 was demonstrated. In the '6-in-1' group, lower post-primary and greater post-booster rSBA-MenC GMTs suggest B-memory cell priming may be favored by this vaccine over plasma cell induction. Furthermore, greater immunogenicity of TT conjugates used in both primary and booster vaccines in this group may be important.