Aim: To examine the validity of published resting energy expenditure (REE) equations in Greek adults, and if indicated, develop new cohort-specific predictive REE equations. Methods: Indirect calorimetry and anthropometric data were obtained from 226 adult volunteers of diverse age groups and body mass index ranges (18–60 years, 16.6–67.7 kg·m–2). Measured REE was compared to preexisting prediction equations via correlation, regression, and Bland-Altman analysis. Then, cohort-specific REE equations were developed using curve estimation and nonlinear regression. To reduce type I error, presently derived equations were validated by splitting the sample into a training and validation group. Results: Preexisting equations over-predicted in-cohort REE. Equations by Livigston and Kohlstadt were most accurate at the individual level (63% accuracy), while formulas by Owen and collaborators elicited highest accuracy at the group level (–1.8% bias). Bland-Altman analysis showed proportional bias for most equations. Currently developed equations showed highest overall accuracy with 70% at the individual and group level (1.0% bias), with small differences between measured and predicted REE values (mean, 95% CI 36 [–15 to 88] kcal·day–1). Conclusion: Data indicate currently developed equations to be the most accurate and valid for estimating REE in Greek adults. Further studies should examine the developed equations in an independent sample.