Sex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as compulsive use.Large populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline alcohol self-administration, motivation to self-administer alcohol, and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study.We found a significant role of sex in alcohol-related behaviors with females showing higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats. Motivation to self-administer alcohol was higher in male rats and correlated positively with punishment-resistance. In contrast, punishment resistance in females was predicted by corticosterone levels. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor.Our results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.