BACKGROUND: Enzymes have received increasing attention as biocatalysts. The poly(lactic) acid (PLA) has been widely employed in biomedical applications and PLA synthesis by a 'green route' is of particular interest. Here the aim is to prepare PLA using lipases, focusing on optimization of the procedure. The effects of the type and concentration of lipase, type of reaction, solvent, and time on the recovery of solid polyester, conversion rate and molecular weight have been explored. Pseudomonas cepacia (PCL), Porcine pancreatic lipase (PPL) and immobilized CAL-B were used as biocatalysts. RESULTS: CAL-B was the most effective biocatalyst, with 60% LA conversion and 55% recovered solid polymer; PCL and PPL gave rise to poor recovery of polymer. A novel thermal treatment was successfully employed to enhance the molecular weight Mn of PLA. CONCLUSIONS: This work offers a set of optimal conditions to synthesize PLA as a function of the lipase used. Information of this nature is currently not available in the literature, thus the findings here are a valuable tool for any researcher in this topic and a state-of-the-art contribution in terms of the best biocatalyst and the best conditions for PLA synthesis. (C) 2008 Society of Chemical Industry