Continuous processing of reagents allows high reaction yields and better operational process control, allied with cost reduction compared to batch mode. In this work, a packed-bed reactor (PBR) system using Novozym 435 for enzymatic ring-opening polymerization (e-ROP) of ɛ-caprolactone (ɛ-CL) with dichloromethane asa cosolvent in supercritical CO2 (scCO2) or in n-butane media, was investigated. The reactions carried out in scCO2 reached yields above 93wt%, average molecular weight (Mn) of up to 31.2kDa and polydispersity (Đ) from 1.4 to 1.6 for only 15min processing. The apparent monomer conversion rate constant (kapp) ranged from 0.094 to 0.180min−1. Otherwise, reactions performed with n-butane provided yields above 80wt%, Mn values of 25.4kDa and Đ in the range of 1.4–1.6, also obtained for 15min of reaction. The maintenance of high yields and molecular weights for up to 6 enzymatic reuses were obtained for both systems studied.