The outcomes of atrial fibrillation (AF) seem to be variable between males and females. We therefore aimed to determine sex differences in weight loss, cardiorespiratory fitness gain, and recurrence and progression of AF following risk factor management. Of 1415 consecutive patients referred for electrophysiology management of AF, 825 had a body mass index of ≥27 kg/m2; after exclusions, 355 (males, 234; females, 121) were offered risk factor management and participation in a tailored exercise program. Females were older than males (65.5±10.4 versus 62.5±10.6 years; P=0.013) with a higher body mass index (34.1±5.4 versus 32.6±4.1 kg/m2; P=0.003) and more commonly paroxysmal AF (67.8% versus 48.3%; P<0.001). There was no sex difference in clinic attendance (58.7% versus 60%; P=0.82), weight loss (P=0.86), fitness gain (P=0.44), or improvement in AF symptoms (P=0.35). Weight loss (≥10% compared with <10%) was associated with lower total AF recurrence in males (hazard ratio, 0.41 [95% CI, 0.23-0.73]) and females (hazard ratio, 0.41 [95% CI, 0.20-0.83]). Fitness gain (≥2 metabolic equivalents compared with <2 metabolic equivalents) was associated with lower total AF recurrence in females (hazard ratio, 0.13 [95% CI, 0.05-0.30]) but not in males (hazard ratio, 0.63 [95% CI, 0.38-1.04]; P=0.002). There was a trend toward more reversal from persistent to paroxysmal AF in males compared with females (21.8% versus 14.0%; P=0.079). Males and females with AF demonstrate a similar degree of weight loss and fitness gain through structured risk factor management. However, fitness had a much greater benefit for total arrhythmia recurrence in females compared with males, whereas there was a trend toward more AF reversal in males. URL: https://anzctr.org.au; Unique identifier: ACTRN12614001123639.