Bispectral index (BIS), a useful marker of anaesthetic depth, is calculated by a statistical multivariate model using nonlinear functions of electroencephalography-based subparameters. However, only a portion of the proprietary algorithm has been identified. We investigated the BIS algorithm using clinical big data and machine learning techniques. Retrospective data from 5,427 patients who underwent BIS monitoring during general anaesthesia were used, of which 80% and 20% were used as training datasets and test datasets, respectively. A histogram of data points was plotted to define five BIS ranges representing the depth of anaesthesia. Decision tree analysis was performed to determine the electroencephalography subparameters and their thresholds for classifying five BIS ranges. Random sample consensus regression analyses were performed using the subparameters to derive multiple linear regression models of BIS calculation in five BIS ranges. The performance of the decision tree and regression models was externally validated with positive predictive value and median absolute error, respectively. A four-level depth decision tree was built with four subparameters such as burst suppression ratio, power of electromyogram, 95% spectral edge frequency, and relative beta ratio. Positive predictive values were 100%, 80%, 80%, 85% and 89% in the order of increasing BIS in the five BIS ranges. The average of median absolute errors of regression models was 4.1 as BIS value. A data driven BIS calculation algorithm using multiple electroencephalography subparameters with different weights depending on BIS ranges has been proposed. The results may help the anaesthesiologists interpret the erroneous BIS values observed during clinical practice.