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Experimental evidence suggests that females (vs. males) may be more sensitive to and derive greater reinforcement from the sensory aspects of combustible cigarette smoking (e.g., flavor, taste). However, it is unknown if there are similar sex differences in the appeal of flavored e-cigarettes. Young adult male (N = 65) and female (N = 35) e-cigarette users (mean age = 25.4; 53% current smokers) attended 1 laboratory session in which they self-administered standardized e-cigarette doses according to a Flavor (fruit vs. tobacco vs. menthol) × Nicotine (6 mg/mL vs. 0 mg/mL) × Voltage (3.3 V vs. 4.3 V) within-participant fully crossed factorial design. Following each trial, participants completed ratings of appeal (mean of liking, disliking [reverse scored], and willingness-to-use-again ratings). Sex was tested as a between-subjects moderator of the effects of flavor on appeal. There was a significant interaction between sex and flavor for e-cigarette appeal (p < .001). In males, fruit-flavored e-cigarettes generated greater appeal than menthol and tobacco (ps < .001). In females, both fruit- and menthol-flavored e-cigarettes generated greater appeal than tobacco (ps < .001), but there was no significant difference between fruit- and menthol-flavored e-cigarettes (p = .40). The findings of this study suggest that males prefer fruit-flavored e-cigarettes, and females prefer both menthol- and fruit-flavored e-cigarettes. The impact of regulatory policies targeting e-cigarette flavors in the population may vary by sex.