Immobilized lipase B from Candida antarctica (Novozym® 435, N435) was utilized as part of a chemoenzymatic strategy for the synthesis of branched polyesters based on a cyclotetrasiloxane core in the absence of solvent. Nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were utilized to monitor the reactions between tetraester cyclotetrasiloxanes and aliphatic diols. The enzyme-mediated esterification reactions can achieve 65–80% consumption of starting materials in 24–48 h. Longer reaction times, 72–96 h, resulted in the formation of cross-linked gel-like networks. Gel permeation chromatography of the polymers indicated that the masses were M_w = 11 400, 13 100, and 19 400 g mol⁻¹ for the substrate pairs of C₇D₄ ester/octane-1,8-diol, C₁₀D₄ ester/pentane-1,5-diol and C₁₀D₄ ester/octane-1,8-diol respectively, after 48 h. Extending the polymerization for an additional 24 h with the C₁₀D₄ ester/octane-1,8-diol pair gave M_w = 86 800 g mol⁻¹. To the best of our knowledge this represents the first report using lipase catalysis to produce branched polymers that are built from a cyclotetrasiloxane core.