Researchers encounter challenges that require making complex professional decisions. Strategies such as seeking help and anticipating consequences support decision-making in these situations. Existing evidence on a measure of professional decision-making in research that assesses the use of decision-making strategies revealed that NIH-funded researchers born outside of the U.S. tended to score below their U.S. counterparts. To examine potential explanations for this association, this study recruited 101 researchers born in the United States and 102 born internationally to complete the PDR and measures of basic personal values, values in scientific work, discrimination between the seriousness of rules in research, exposure to unprofessional research practices, and acculturation to American culture. Several variables were associated with PDR scores—discrimination between types of rules in research, exposure to unprofessional research practices, acculturation, and the basic personal values of power, security, and benevolence. However, only security, benevolence, acculturation, and rule discrimination were also associated with nation of origin. In multivariate models, the variance explained by these variables in accounting for the association of nation of origin and PDR scores was somewhat overlapping, thus, only security and benevolence remained as unique, statistically significant predictors. Thus, this study identified some important variables in the association of nation of origin and PDR, but more research is needed. In a secondary analysis to examine the “clinical significance” of scores on the PDR, this study examined aggregated PDR score data from the present sample and past samples of investigators. This analysis identified scores that may suggest a concern versus those scores that may be interpreted as excellent, proficient, or marginal. Implications for training and mentoring, along with considerations for future research are discussed.