This study had three purposes, all related to evaluating energy expenditure (EE) prediction accuracy from body-worn accelerometers: (1) compare linear regression to linear mixed models, (2) compare linear models to artificial neural network models, and (3) compare accuracy of accelerometers placed on the hip, thigh, and wrists. Forty individuals performed 13 activities in a 90 min semi-structured, laboratory-based protocol. Participants wore accelerometers on the right hip, right thigh, and both wrists and a portable metabolic analyzer (EE criterion). Four EE prediction models were developed for each accelerometer: linear regression, linear mixed, and two ANN models. EE prediction accuracy was assessed using correlations, root mean square error (RMSE), and bias and was compared across models and accelerometers using repeated-measures analysis of variance. For all accelerometer placements, there were no significant differences for correlations or RMSE between linear regression and linear mixed models (correlations: r = 0.71-0.88, RMSE: 1.11-1.61 METs; p > 0.05). For the thigh-worn accelerometer, there were no differences in correlations or RMSE between linear and ANN models (ANN-correlations: r = 0.89, RMSE: 1.07-1.08 METs. Linear models-correlations: r = 0.88, RMSE: 1.10-1.11 METs; p > 0.05). Conversely, one ANN had higher correlations and lower RMSE than both linear models for the hip (ANN-correlation: r = 0.88, RMSE: 1.12 METs. Linear models-correlations: r = 0.86, RMSE: 1.18-1.19 METs; p < 0.05), and both ANNs had higher correlations and lower RMSE than both linear models for the wrist-worn accelerometers (ANN-correlations: r = 0.82-0.84, RMSE: 1.26-1.32 METs. Linear models-correlations: r = 0.71-0.73, RMSE: 1.55-1.61 METs; p < 0.01). For studies using wrist-worn accelerometers, machine learning models offer a significant improvement in EE prediction accuracy over linear models. Conversely, linear models showed similar EE prediction accuracy to machine learning models for hip- and thigh-worn accelerometers and may be viable alternative modeling techniques for EE prediction for hip- or thigh-worn accelerometers.