The compatibility between several dressing materials and a recombinant human vascular endothelial growth factor (rhVEGF) topical methylcellulose gel formulation was investigated. The dressings being studied were Adaptic, Non-stick Dressing, Conformant 2, Opsite and Tegapore. The criteria to select a compatible dressing include protein stability, absence of leachables from the dressing, and ability to retain gel on wound. An LC-MS method with sample treatment using cellulase was developed to determine protein oxidation in gel formulations. Results showed that rhVEGF was significantly oxidized by Adaptic dressing in 24 h. Protein oxidation was likely due to the peroxides, as determined by FOX assay, released into the protein solution from the dressing. Furthermore, Adaptic dressing caused protein adsorption loss, formation of high MW protein adducts, and released leachables as determined by RP-HPLC, LC-MS, and SEC. No protein oxidation or loss was observed after exposure to the other four alternative dressings. However, unknown leachables were detected in the presence of Opsite and Non-stick Dressing. The pore sizes of the Conformant 2 and Non-stick dressings were too large to hold the topical gel within the wound area, making them unsuitable for patient use. No rhVEGF bioactivity loss was observed in the presence of Tegapore. In conclusion, Tegapore was considered suitable for the rhVEGF topical gel.