The purpose of this study was to examine the gender effect of daily consumption of a thermogenic drink (TD) containing caffeine, epigallocatechin gallate, and taurine. In a single-blind, matched-pairs, placebo-controlled study, 60 participants (n = 30 men and n = 30 women) were matched in a balanced fashion according to age and body mass. Participants completed determination of body composition, resting energy expenditure (REE), and serum levels of glycerol and free fatty acids before and after ingesting either 336 mL of a TD or a noncaloric, noncaffeinated placebo (PLA). Participants were supplemented daily with 336 mL of either the TD or PLA and repeated identical testing procedures on day 28. Area under the curve (AUC) analysis on days 0 and 28 were calculated for all blood variables (e.g., glycerol and free fatty acids) and analyzed with REE, respiratory exchange ratio, dietary records, and body composition with separate repeated-measure analyses of variance. On days 0 and 28, REE AUC (p , 0.001) was greater in all men compared with in women. Women ingesting the TD had significantly greater free fatty acid AUC values (p = 0.002) when compared with those of men. A significant interaction for glycerol AUC (p = 0.02) revealed greater glycerol concentrations in the male PLA group, which decreased in all other groups from days 0 to 28. The male TD group lost significantly more percent body fat (p = 0.02) than did the female PLA group. The popularity of thermogenic drinks to promote weight loss and body composition changes has grown exponentially. Gender differences after drink ingestion may impact the resulting adaptations and how successful their inclusion impacts weight loss and body-composition changes in those following a regular diet and exercise program.