National Institutes of Health principal investigators reported their perceptions of the ethical defensibility, prevalence in their field, and their personal willingness to engage in questionable research practices (QRPs). Using ethical defensibility ratings, an exploratory factor analysis yielded a two-factor solution: behaviors considered unambiguously ethically indefensible and behaviors whose ethical defensibility was more ambiguous. In addition, increasing perceptions that QRPs affect science predicted reduced acceptability of QRPs, whereas increasing beliefs that QRPs are normative or necessary for career success predicted increased acceptability of QRPs. Perceptions that QRPs are risky were unrelated to QRP acceptability but predicted reduced extramural funding (i.e., researchers' lifetime extramural grants and total funding secured). These results identify risk (i.e., beliefs that QRPs are normative to stay competitive in one's field) and protective factors (i.e., beliefs that QRPs have a significant negative impact on society) related to QRP endorsement that could inform educational interventions for training research scientists.