This study proposes a flexible intelligent algorithm for assessment and optimization of demographic features on integrated health, safety, and environment and ergonomics (HSEE)-ISO systems among operators of a gas transmission refinery. To achieve the objectives of this study, standard questionnaires with respect to HSEE and ISO standards are completed by 80 operators. Demographic features include age, education, gender, weight, stature, marital status, and work type. The average results for each category of HSEE are used as inputs and effectiveness of ISO systems (ISO 18000, ISO 14000, and ISO 9000) are used as output for the intelligent algorithm. Artificial Neural Networks (ANN) and Adaptive Neuro Fuzzy Inference System (ANFIS) in addition to conventional regression are used in this paper. Result shows the applicability and superiority of the flexible intelligent algorithm over conventional methods through mean absolute percentage error (MAPE). Computational results show that the proposed ANN performs better than ANFIS and conventional regressions based on its relative error. Finally, the optimum mix of demographic variables from viewpoint of HSEE and ISO are identified. This is the first study that proposes a flexible intelligent algorithm for assessment of optimum mix of demographic features for HSEE and ISO systems in a complex system such as a gas transmission refinery. (C) 2013 Elsevier Ltd. All rights reserved.