Polylactic acid and polylactic-co-glycolic acid are biocompatible and biodegradable polymers with wide utility for the design of controlled release systems for drugs. Regarding intraocular application, polymeric sustained-drug release systems are being studied to treat vitreoretinal diseases. Our work aimed to compare the influence of two implant manufacturing techniques, compression and hot molding, on the in vitro degradation of the polymeric matrices and on the release of dexamethasone acetate. The results showed that the manufacturing technique highly influences degradation and drug release processes. The compressed systems degraded faster and allowed one faster release of the drug.