When governments and healthcare providers offer people cash rewards for weight loss, an assumption is that cash rewards are versatile, working equally well for everyone – for example, for all genders. No research to date has tested for gender difference in response to financial incentives for weight loss. We show in an randomized controlled trial (RCT) (n = 472) that cash incentives for weight loss only worked for males. The RCT consisted of a 3-month, self-administered online weight loss program. Offering a US$150 incentive for a 5% weight loss more than tripled the proportion of males who were successful, compared with a no-incentive Control arm (20.9% vs. 5.9%). On average, males in the incentive arm lost 2.4% of weight over 3 months, compared with 0.9% in the Control arm. The same incentive had no such effect on females: The average weight loss in the incentive arm was not significantly different than in the Control (1.03% and 1.44%, respectively), nor was the proportion of participants meeting the 5% weight loss goal (8.6% and 8.7%, respectively). This study shows that males respond better than females to financial incentives for weight loss.