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Laboratory experiments were used to estimate the hydraulic performance of emitters, i.e., the emitter flow variation (qvar) and manufacturer’s coefficient of variation (CVm), by measuring the discharge of different labyrinth-channel emitters at different operating pressures (P) and water temperatures (T). Considering the importance of the structural parameters of the labyrinth-channel emitters in drip irrigation design, which has been experimentally confirmed, artificial neural network (ANN) and gene expression programming (GEP) models were developed to predict qvar and CVm. The ANN and GEP models were trained and tested using structural parameters (including the number, height (H), and spacing of trapezoidal units and the flow path width and length) of different labyrinth-channel emitters, P and T as the input variables, and qvar and CVm as the outputs. Statistical criteria, including the coefficients of correlation (r), relative root-mean-square error (RRMSE), and mean absolute error (MAE), were used to examine the accuracy of the developed models. The ANN models exhibited good correlation with experimental values, with high r values 0.995 and 0.969 for qvar and 0.997 and 0.947 for CVm in the training and testing processes, respectively. The ANN models had lower RRMSE and MAE values than the GEP models. Furthermore, H was the dominant variable for obtaining the most accurate prediction model. The results confirm that the ANN models are superior to the GEP models for the prediction of the hydraulic performance of emitters.