We conducted the first pooled analysis of two randomised controlled vaccine trials on experimental pneumococcal serotype 6B carriage, registered in Malawi (PACTR202008503507113) and the UK (ISRCTN45340436). This post-hoc exploratory study examined the sex-based differences in carriage, vaccine efficacy and vaccine-induced responses. PCV-13 reduced colonisation by 76% (p < 0.001) with non-significant interaction by sex (RR = 1.549, p = 0.413). Females showed a higher carriage rate than males (28% vs. 19%, p = 0.066). Baseline anti-6B Capsular Polysaccharide Immunoglobulin G (IgG) titres were higher in females, significantly in Malawi (2.62 µg/ml vs males 2.05 µg/ml, p = 0.015). Post-vaccination titres did not differ by sex. The pooled fold change in IgG pre-post vaccination, was higher in vaccinated females (5.47 vs 3.30, p = 0.053). This analysis demonstrates the utility and challenges of integrating CHIM data between diverse settings to evaluate vaccine efficacy, describe inter-setting differences, investigate biological and immunological factors influencing protection against pneumococcal carriage and ultimately inform future vaccine development strategies.