Designing effective direct mail pieces is considered a key success factor in direct marketing. However, related published empirical research is scarce while design recommendations are manifold and often conflicting. Compared with prior work, our study aims to provide more elaborate and empirically validated findings for the effects of direct mail design characteristics by analyzing 677 direct mail campaigns from non-profit organizations and financial service providers. We investigate the effects of (1) various envelope characteristics and observable cues on opening rates, and (2) characteristics of the envelope content on the keeping rates of direct mail campaigns. We show that visual design elements on the outer envelope – rather than sender-related details – are the predominant drivers of opening rates. Factors such as letter length, provision of sender information in the letter, and personalization positively influence the keeping rate. We also observe that opening and keeping rates are uncorrelated at the campaign level, implying that opening direct mail pieces is only a necessary condition for responding to offers, but not per se a driver of direct mail response.