Background: Although plenty of evidence indicates that weight loss maintainers are highly physically active, studies focusing on the sex-specific differences in activity levels between maintainers and regainers are scarce. The authors aimed to investigate sex-specific differences in activity patterns in a cohort of Mediterranean maintainers and regainers. Methods: Sample includes 756 participants of the MedWeight registry (60.5% women), aged 18–65 years, who lost ≥10% of their initial weight, and either maintained their loss for ≥12 months or regained it. Participants completed a series of questionnaires, including demographics and weight history. Activity levels were evaluated with the International Physical Activity Questionnaire-short version. Results: Maintainers of both sexes were, in total, more active than their same-sex regainers. When specific activities were considered, women maintainers spent more time walking than regainers (P adjusted = .02), whereas men maintainers spent more time in vigorous activities (P adjusted = .001) and walking than regainers (P adjusted = .001). Modest increments in activity of sex-relevant intensity were associated with increased odds for maintenance. Conclusions: Maintainers attained a more active lifestyle than their same-sex regainers, involving more walking for both sexes and more vigorous activities for men. The detected differences, according to activity intensity, support that activity patterns associated with successful weight loss are distinguishable between sexes.