A novel approach for determining macromolecule baselines at medium TE was proposed. Inversion recovery was combined with spectral editing to acquire six sets of MRS data using two editing frequencies and three long inversion times (TI). Macromolecule signals were essentially invariant across the three long TIs but metabolite signal amplitudes were significantly modulated by TI. By simultaneously fitting the six sets of data, metabolite and macromolecule signals were reliably separated without using empirical constraints on the amplitudes of the spline baselines. Compared to existing techniques, this approach exploits both T1 and T2 differences between metabolites and macromolecules.