This study explores separation orthogonality with respect to comprehensive two-dimensional gas chromatography (GC x GC) for a range of different column polarities in the first dimension (1D), with two second dimension (2D) column types. Systematic variation in the net polarity of the first dimension allows the effect of column phase relative polarity on analyte retention in both the first and second dimensions to be evaluated. First dimension polarity manipulation significantly affects elution temperature (T(e)) of the analytes. This alters the magnitude of retention on the second dimension, and the extent of utility of separation space. By use of retention factor/temperature data in single column experiments, along with 1D T(e) data, retention on the 2D column can be estimated. This allows the two-dimensional separation to be predicted, and compared with experimental data. Predicted GC x GC peak positions corresponded favourably with the experimentally derived chromatograms, yielding a simple approach for predicting two-dimensional separations, using unique column set combinations.