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Objective Over the last decades, numerous school-based smoking prevention programs have been launched internationally. However, there has been limited research on the differential effect of sex in response to the implementation of school-based smoking prevention interventions. The aim of this study was to examine sex differences in the attitudes towards a school-based smoking prevention intervention. Specifically, the research questions explore whether there are sex differences in the attitudes towards the three main components; 1) Smoke-free school grounds 2) Smoke-free curriculum, and 3) Smoke-free agreement. Methods We used data from the X:IT II intervention study with 46 elementary schools collected in 2017-2018. The X:IT II intervention is a school-based multicomponent smoking prevention intervention targeted all students attending grade 7 to 9 (13- to 15-year-olds). Data were collected by electronic questionnaires completed by students at first follow-up. Results We found that compared to boys, girls were significantly more positive towards the implementation of smoke-free school grounds, both concerning teachers smoking (66 % vs. 53.5 %) and students smoking (61.3 % vs. 51.9 %) and toward the smoke-free curriculum (79.5 % vs. 71.9 %). No statistically significant differences between boys and girls could be observed in the proportion of students signing the smoke-free agreement, nor in their attitudes towards the agreement. Conclusions This study showed that there were, to some extent, sex differences in the attitudes towards components in the X:IT II intervention study. Our findings highlight the importance of considering sex differences in future health prevention initiatives.