Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study we therefore investigated neural cue-reactivity in a sample of male (n=28) and female (n=27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p<0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in males and females, visual alcohol-cues induced significantly stronger striatal activation in male compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol-cue reactivity studies should, in addition to including both males and females, include different types of cues (e.g. stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity. This article is protected by copyright. All rights reserved.