A solid understanding of fractions is the cornerstone for acquiring proficiency with rational numbers and paves the way for learning advanced mathematical concepts, such as algebra. Fraction difficulties limit not only students' educational and vocational opportunities but also their ability to solve everyday problems. Students who exit 6th grade with inadequate understanding of fractions may experience far-reaching repercussions that lead to lifelong avoidance of mathematics. This paper presents the results of a randomized controlled trial (RCT) focusing on the first two cohorts of a larger efficacy investigation aimed at building fraction sense in students with mathematics difficulties. Teachers implemented an evidence-informed fraction sense intervention (FSI) within their 6th-grade intervention classrooms. The lessons draw from research in cognitive science as well as mathematics education research. Employing random assignment at the classroom level, multilevel modeling revealed a significant effect of the intervention on posttest fractions scores, after controlling for pretest fractions scores, working memory, vocabulary, proportional reasoning, and classroom attentive behavior. Students in the FSI group outperformed their counterparts in the control group with noteworthy effect sizes on most fraction measures. Challenges associated with carrying out school-based intervention research are addressed. [This is the online first version of an article published in "Journal of Experimental Child Psychology."]