In 2010 Skowronski and colleagues reported that seasonal influenza vaccine appeared to increase the risk of pandemic influenza H1N1 2009 (pH1N1) infection during the first pandemic wave in Canada [1]. They suggested a number of possible explanations for their unexpected finding: firstly, that the results were an artefact of selection bias or confounding; secondly, that the results were due to partial mediation through a biological mechanism; and thirdly, that the results were due to a direct immune mechanism, such as antibody dependent enhancement [1]. In a recent paper in Vaccine, Rosella and colleagues have investigated in detail the first of these possibilities, confirming that it is unlikely an unidentified confounder could have explained the findings [2].