Background: In 2011, 10-valent pneumococcal conjugate vaccine (PCV10) replaced PCV7 in The Netherlands. We aimed to assess the impact of this switch on non-invasive pneumococcal disease in primary care across various age-groups, including pneumonia-bronchitis, otitis media (OM) and sinusitis with and without considering pre-PCV10 secular trends. Methods: Electronic records of 397,441 individuals included in a regional primary care database from July 2006 to June 2016 were extracted (2,408,762 person-years). We fitted interrupted time-series on annual incidence rates (IR) of primary care diagnosed pneumonia-bronchitis, OM and sinusitis episodes per age-group. We performed these two types of analyses, comparing; 1) the post-PCV10 observed versus expected trend if PCV10 had not been implemented and pre-PCV10 secular trends had continued 2), the pre- versus post-PCV10 observed, model fitted trend. The latter assumes no secular trend. Incidence rate ratios (IRR) were calculated using both methods. Results: We found significant reductions following PCV10 introduction with both analysis methods for pneumonia-bronchitis in the pediatric and adult age-groups, for sinusitis in the age-group 20–50 years and for OM, the effect across various age-groups are uncertain given contradictory results. For other outcomes and age-groups, the effect estimates were not consistent across the two-method used and heavily depended on the strength of the underlying trend. No consistent effects were observed in the elderly population, considering the two methods used. Conclusion: Our study supports some direct and indirect-effect of PCV10 introduction on non-IPD, mainly on pneumonia-bronchitis, but estimates heavily depend on the method of analysis used. Estimates from the two different approaches may differ substantially if underlying trends are strong.