Poor instruction has been cited as a primary cause of attrition from STEM majors and a major obstacle to learning for those who stay [Seymour and Hewitt [1997]. Talking about leaving: Why undergraduates leave the sciences. Boulder, CO: Westview]. Using a double-blind design, this study tests the hypothesis that the lack of explicit instructions in scientific inquiry skills is a major factor in both low STEM retention and academic underperformance. This project delivered supplemental instruction to students in a laboratory-based undergraduate biology course (n = 314) that was derived either from cognitive task analyses (CTAs) conducted with expert biologists (treatment) or was authored and delivered by an award-winning biology instructor (control). Students receiving traditional instruction were almost six times more likely to withdraw from the course than students in the treatment condition (8.1% vs. 1.4% of initial enrollment). Of the students who completed the course, those who received the CTA-based instruction demonstrated significantly higher levels of performance in the discussion section of their written laboratory reports. Significantly higher performances were seen specifically in the areas of analyzing data to formulate valid conclusions, considering alternative explanations, consideration for the limitations of the experimental design and implications of the research.