The water-gas shift reaction occurs competitively to the main reaction of the Ir-catalysed methanol carbonylation process. To study the effect of seven factors including temperature, pressure, iridium, ruthenium, methyliodide, methyl acetate and water concentrations on the formation of hydrogen and carbon dioxide as a result of the water-gas shift reaction and other side reactions in the carbonylation of methanol to acetic acid, the experimental design method combined with response surface methodology (RSM) was utilised. Central composite design at five levels (with alpha = 1.63) was used to design experiments. A quadratic model that included the main and interaction effects of variables for H-2 and CO2 formation was developed. For two responses, R-2 was in reasonable agreement "Adj-R-2". Furthermore, statistical tests confirmed the accuracy and the precision of models developed in this research. For CO2 formation, pressure, iridium and methyl iodide concentrations and for H-2 formation, water and iridium concentrations had the most pronounced effects. Optimum conditions to minimise H-2 and CO2 and CH4 formation were determined as follows: temperature of 189 degrees C, pressure of 32.0 bar, iridium content of 859 ppm, ruthenium concentration of 528 ppm, methyl iodide content of 8.68 wt%, methyl acetate concentration of 23.9 wt% and water content of 6.49 wt%. Ultimately, an experiment at optimum conditions revealed satisfactory agreement between the experimental and predicted data. Crown Copyright (c) 2011 Published by Elsevier Ltd. All rights reserved.