Background: When the resting energy expenditure (REE) of overweight and obese adolescents cannot be measured by indirect calorimetry, it has to be predicted with an equation. Objective: The aim of this study was to examine the validity of published equations for REE compared with indirect calorimetry in overweight and obese adolescents. Design: Predictive equations based on weight, height, sex, age, fatfree mass (FFM), and fat mass were compared with measured REE. REE was measured by indirect calorimetry, and body composition was measured by dual-energy X-ray absorptiometry. The accuracy of the REE equations was evaluated on the basis of the percentage of adolescents predicted within 10% of REE measured, the mean percentage difference between predicted and measured values (bias), and the root mean squared prediction error (RMSE). Results: Forty-three predictive equations (of which 12 were based on FFM) were included. Validation was based on 70 girls and 51 boys with a mean age of 14.5 y and a mean (6SD) body mass index SD score of 2.93 6 0.45. The percentage of adolescents with accurate predictions ranged from 74% to 12% depending on the equation used. The most accurate and precise equation for these adolescents was the Molnar equation (accurate predictions: 74%; bias: –1.2%; RMSE: 174 kcal/d). The often-used Schofield-weight equation for age 10–18 y was not accurate (accurate predictions: 50%; bias: +10.7%; RMSE: 276 kcal/d). Conclusions: Indirect calorimetry remains the method of choice for REE in overweight and obese adolescents. However, the sex-specific Molnar REE prediction equation appears to be the most accurate for overweight and obese adolescents aged 12–18 y. This trial was registered at www.trialregister.nl with the Netherlands Trial Register as ISRCTN27626398.