Effective strategies are required to reduce the prevalence of overweight and obesity however the effectiveness of current weight loss programs is variable. One contributing factor may be the difference in weight loss success between males and females. A systematic review was conducted to determine whether the effectiveness of weight loss interventions differs between males and females. Randomised controlled trials published up until March 2014 were included. Effect sizes (Hedge’s g) were used to examine the difference in weight loss between males and females. A total of 58 studies met eligibility criteria with 49 studies of higher quality included in the final data synthesis. Ten studies that directly compared weight loss in males and females reported a significant sex difference. Nine of these reported that males lost more weight than females however females also lost a significant amount of weight. Analysis of effect sizes found small differences in weight loss favouring males for both diet (g=0.323) and diet plus exercise (g=0.202) interventions. There is little evidence from this review to indicate that males and females should adopt different weight loss strategies. Current evidence supports moderate energy restriction in combination with exercise for weight loss in both males and females.