Past studies on the differential effects of active learning based on students' prior preparation and knowledge have been mixed. The purpose of the present study was to ask whether students with different levels of prior preparation responded differently to laboratory courses in which a guided-inquiry module was implemented. In the first study, we assessed student scientific reasoning skills, and in the second we assessed student experimental design skills. In each course in which the studies were conducted, student gains were analyzed by pretest quartiles, a measure of their prior preparation. Overall, student scientific reasoning skills and experimental design skills did not improve pretest to posttest. However, when divided into quartiles based on pretest score within each course, students in the lowest quartile experienced significant gains in both studies. Despite the significant gains observed among students in the lowest quartile, significant posttest differences between lowest and highest quartiles were observed in both scientific reasoning skills and experimental design skills. Nonetheless, these findings suggest that courses with guided-inquiry laboratory activities can foster the development of basic scientific reasoning and experimental design skills for students who are least prepared across a range of course levels and institution types.