A method for the simultaneous separation and determination of Nb(V) and Ta(V) as ternary complexes formed with 2-(5-bromo-2-pyridylazo)-5-[ N-propyl- N-(3-sulfopropyl)amino]phenol (PAPS) and citrate was developed using ion interaction reversed-phase high-performance liquid chromatography (HPLC) on a C18 column. An artificial neural network (ANN) in combination with a reduced factorial experimental design was utilised to optimise the mobile phase compositions and the conditions used for pre-column complex formation. Under the optimum conditions determined by the ANN, the Nb(V) and Ta(V) complexes were eluted within 5 min. The detection limits (signal to noise ratio = 3, detection wavelength 600 nm) for Nb(V) and Ta(V) were 0.03 and 0.40 μg/l, respectively, which correspond to 0.03 and 0.40 μg/g in the solid samples. The method was applied to the analysis of geological samples and the results obtained by the HPLC method agreed well with the results obtained by ICP-MS and also with the certified values.