The biocompatibility of autocatalyzed poly(ortho ester) (POE₇₀LA₃₀), a viscous, hydrophobic, bioerodible polymer, was investigated. POE₇₀LA₃₀ was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE₇₀LA₃₀ bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE₇₀LA₃₀ biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE₇₀LA₃₀ were reproducible and well tolerated. POE₇₀LA₃₀ triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE₇₀LA₃₀ appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance.