This study was conducted using the first-lactation records of 1092 Vrindavani crossbred cattle to compare the relative efficiency of an artificial neural network (ANN) versus multiple linear regression for predicting the first-lactation 305-day milk yield (FL305DMY). The two input sets used for predicting FL305DMY in the study were input set-1: first four monthly test-day milk yields, age at first calving, and peak milk yield; and input set-2: first four monthly milk yields, age at first calving, and peak milk yield. The ANN was trained using a backpropagation algorithm based on Bayesian regularisation, and the algorithm was tested using four sets of training and test data at ratios of 66.67:33.33, 75:25, 80:20, and 90:10. The results revealed that the coefficient of determination showed no regular trend with decreasing the test dataset. Nevertheless, the observed values were highest for the 90:10 ratio of training-test data for both input sets, with the lowest root mean square error. The ANN model outperformed the multiple linear regression model when predicting FL305DMY, with an accuracy of 79.09% for input set-1 and 83.67% for input set-2, with the lowest root mean square error values for both input sets. Therefore, the ANN model can be used as an alternative technique to predict FL305DMY in Vrindavani cows.