Introduction This study developed a new Professional Decision-Making in Medicine Measure that assesses the use of effective decision-making strategies: seek help, manage emotions, recognize consequences and rules, and test assumptions and motives. The aim was to develop a content valid measure and obtain initial evidence for construct validity so that the measure could be used in future research or educational assessment. Methods Clinical scenario-based items were developed based on a review of the literature and interviews with physicians. For each item, respondents are tasked with selecting two responses (out of six plausible options) that they would choose in that situation. Three of the six options reflect a decision-making strategy; these responses are scored as correct. Data were collected from a sample of 318 fourth-year medical students in the United States. They completed a 16-item version of the measure (Form A) and measures of social desirability, moral disengagement, and professionalism attitudes. Professionalism ratings from clerkships were also obtained. A sub-group (n = 63) completed a second 16-item measure (Form B) to pilot test the instrument, as two test forms are useful for pre-posttest designs. Results Scores on the new measure indicated that, on average, participants answered 75% of items correctly. Evidence for construct validity included the lack of correlation between scores on the measure and socially desirable responding, negative correlation with moral disengagement, and modest to low correlations with professionalism attitudes. A positive correlation was observed with a clerkship rating focused on professionalism in peer interactions. Conclusions These findings demonstrate modest proficiency in the use of decision-making strategies among fourth-year medical students. Additional research using the Professional Decision-Making Measure should explore scores among physicians in various career stages, and the causes and correlates of scores. Educators could utilize the measure to assess courses that teach decision-making strategies.