The lucrative world of comparative advertising has been attractive to marketers, who seek economic types of persuasive communication. Nevertheless, research in the actual effectiveness of comparative advertising has been inconclusive, contradicting, and insufficient. The increasing importance of comparative advertising in the current competitive global environment requires immediate findings about how comparative advertising can work effectively. This study is the first study to develop an integrated conceptual model of the factors, which influence comparative advertising effectiveness. Particularly, the conceptual model comprehensively indicates that two advertising features (namely, intensity of comparative claims, and source attractiveness) and five characteristics of the ad recipients (namely, NFC, product involvement, gender, familiarity with comparative advertising, and culture) determine the effectiveness of a comparative ad. The study adopts a critical-realist approach and a multi-method design to explore the research topic. The research questions are addressed using qualitative and quantitative data in a cross-cultural approach. Two phases of exploratory interviews conducted in Greece and a series of pilot tests conducted in the UK and Greece inform an extensive experimental study of 820 participants to explore the research questions and test all research hypotheses. The research findings empirically validate the conceptual model of the study in both countries. It is largely confirmed that the above mentioned factors influence claim believability and perceptions of manipulation intent in comparative advertising. Further persuasion effects are also examined. The results of the study contribute to knowledge about comparative advertising effectiveness and provide information and guidance to practitioners on how to develop and implement effective comparative ads. Overall, comparative advertising is a powerful marketing tool, which has to be applied with caution as there are factors which can have a negative impact on comparative advertising effectiveness. The novel findings of this study endow future research with a new avenue to proceed.