Aeration experiments were conducted in a masonry tank to study the effects of operating parameters on standard aeration efficiency (SAE) of a propeller diffused aeration (PDA) system. The operating parameters include the rotational speed of shaft (N), submergence depth (h), and propeller angle (α). The response surface methodology (RSM) and artificial neural network (ANN) were used for modelling and optimizing the standard aeration efficiency (SAE) of a PDA system. The results of the both approaches were compared for their modelling abilities in terms of coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE), computed from experimental and predicted data. ANN models were proved to be superior to RSM. The results indicate that for achieving the maximum standard aeration efficiency (SAE), N, h and α should be 1,000 rpm, 0.50 m, and 12°, respectively. The maximum SAE was found to be 1.711 kg O2/ kWh. The cross-validation results show that the best approximation of optimal values of input parameters for maximizing SAE is possible with a maximum deviation (absolute error) of ±15.2% between the model predicted and experimental values.