A second generation ionic liquid matrix (ILM), N,N-diisopropylethylammonium α-cyano-4-hydroxycinnamate (DEA-CHCA), was developed for the characterization of polar biodegradable polymers. It is compared with five solid matrices typically used for the characterization of these polymers and one other new ILM. It is shown that use of the ILM, DEA-CHCA, allows maximum signal with minimum laser intensity which minimizes polymer degradation. In these conditions, the DEA-CHCA ILM is able to assist in the ionization of analytes in an efficient but soft manner. These qualities produce spectra that allow an accurate and sensitive determination of the number average molecular weights, weight average m.w., and polydispersity index of labile polar polymers. With such polymers, many solid matrices produce spectra showing extensive polymer degradation leading to the underestimation of molecular weights. The distribution of intact analyte peaks obtained with the ILM DEA-CHCA allows for identification of the fine structure of complex copolymers. ILMs were much less susceptible to effects of extraction delay times on molecular weight determination than were solid matrices. The liquid nature of the matrix is an important reason for the outstanding results obtained for labile analyte polymers. No comparable results could be obtained with any known solid matrices or other ILMs. In many cases, the manufacturers' listed molecular weights and polydispersity measurements for biodegradable polymers are determined by size-exclusion chromatography and the data obtained by that method may differ considerably from the high-precision matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results presented here. Copyright © 2009 John Wiley & Sons, Ltd.