The prediction of uncertainties is a growing interest in flow assurance industrial applications, but only few works have been presented on this topic. In this work, an uncertainty quantification and a global sensitivity analysis are performed to quantify the level of confidence in predictions of one-dimensional mechanistic models considering different two-phase flow regimes. A method is proposed for this purpose accounting for the effect of several variables on pressure drop and hold-up predictions by the well-known one-dimensional two-fluid model, such as fluid flow rates, geometry (the inclination angle and the pipe diameter), and fluid properties (density and viscosity); the case of a non-Newtonian shear-thinning fluid behaviour is also considered. Flow pattern transition boundaries, including the stability of the stratified flow regime, are included in this analysis. Monte Carlo simulations were used for the uncertainty quantification while different approaches for the sensitivity analysis (scatter plot, linear regression, the Morris's method, and the Sobol's Method) were used and compared to identify the best tool for this family of models. The Sobol's method appears to be the most convenient approach and a discussion is provided considering different practical cases for gas/liquid and liquid/liquid systems. The most critical input parameters in terms of uncertainty are rigorously identified case by case. A way to reduce the output uncertainty is indicated by the interpretation of the results of the global sensitivity analysis. The conclusions of this analysis gives new insights regarding the degree of uncertainties in predictions of one-dimensional mechanistic models. (C) 2016 Elsevier Ltd. All rights reserved.