Influenza vaccine effectiveness (VE) has to be estimated anew for every season to explore vaccines’ protective effect in the population. We report VE estimates against laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2) and influenza B among children aged 2–17 years, using test-negative design. Pooled data from two German federal states’ surveillance systems for acute respiratory illness from week 40/2012 to 20/2016 was used, yielding a total of 10 627 specimens. Odds ratios and 95% confidence intervals (95% CIs) for the association between laboratory-confirmed influenza and vaccination status were calculated by multivariate logistic regression adjusting for age, sex, illness onset and federal state. VE was estimated as 1-Odds Ratio. Overall adjusted VE was 33% (95% CI: 24·3–40·7). A strong variation of VE between the seasons and subtypes was observed: highest season- and subtype-specific VE of 86·2% (95% CI: 41·3–96·7) was found against A(H1N1)pdm09 in 7–17-year-olds in 2015/16. Low estimates of VE were observed against A(H3N2) in any season, e.g. 1·5% (95% CI: −39·3–30·3) in 2014/15. Estimates showed a tendency to higher VE among 7–17-year-old children, but differences were not statistically significant. Although our findings are common in studies estimating influenza VE, we discussed several explanations for observed low VE.