The authors hypothesized that highly structured course designs, which implement reading quizzes and/or extensive in-class active-learning activities and weekly practice exams, can lower failure rates in an introductory biology course, compared with low-structure course designs that are based on lecturing and a few high-risk assessments. The experimenters controlled for instructor effects by analyzing data from quarters when the same instructor taught the course, exam equivalence with new assessments called the Weighted Bloom’s Index and Predicted Exam Score, and student equivalence using a regression-based Predicted Grade. The authors also tested the hypothesis that points from reading quizzes, clicker questions, and other assignments in highly structured courses inflate. They found no evidence that points from active-learning exercises inflate grades or reduce the impact of exams on final grades. When controlled for variation in student ability, failure rates were lower in a moderately structured course design and were dramatically lower in a highly structured course design. This result supports the hypothesis that active-learning exercises can make students more skilled learners and help bridge the gap between poorly prepared students and their better-prepared peers.