The biocatalytic synthesis of fluorinated polyesters from activated diesters and fluorinated diols has been investigated. The effects of time, continuous enzyme addition, enzyme concentration, and diol chain length were studied to determine the factors that would limit chain extension, such as enzyme inactivation, enzyme specificity, the equilibrium position for the reaction, hydrolytic side reactions, and polymer precipitation. An enzyme screen demonstrated that only Novozym 435, an immobilized lipase from Candida antarctica, was effective in producing the fluorinated polyester. Molecular weight and polydispersity analyses were performed by means of gel permeation chromatography. End group analysis was accomplished through the use of matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. Polymer molecular weight steadily increased and then leveled off after approximately 30 h, with a weight average molecular weight of approximately 1773. The majority of the polymer chains were terminated with either hydroxyl or vinyl groups. Polymers that were synthesized from bulk monomers had higher molecular weights, but high enzyme concentrations were required. Enzyme specificity toward shorter chain fluorinated diols appeared to be the governing factor in limiting chain growth. However, polymer molecular weight increased further (M-w= 8094) when a fluorinated diol that contained an additional methylene spacer between the fluorine atoms and hydroxyl groups was used.