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The present paper explores the relationship between attitudes towards mathematics (ATM) and achievement in college calculus in active learning (AL) and lecture-based (LB) classrooms. Previous work on this relationship has mainly been limited to LB instruction, neglecting the impact of innovative approaches such as AL. Less attention has been paid to the roles played in this relationship by gender, year in college, and initial ATM. Results from a sample of 535 undergraduate students enrolled in 9 AL and 9 LB sections are presented. Data included ATMI surveys’ responses, final grades, and demographics. Correlation and multiple regression analyses were conducted. The influence of instruction on students with low ATM was also examined. Gender and year in college were the main demographic variables considered. Achievement in AL was found to be less dependent on initial ATM in terms of correlation. AL showed higher gains in grades than LB, when controlling for ATM and demographic variables. Effect sizes of AL instruction on grades of students with low ATM were larger than those of students with higher ATM. Furthermore, AL courses had a large effect size (d = 0.81) on female students with lower ATM, confirming its role as a gender equalizer.