Purpose: To investigate microbiologic trends and role of biofilm on periorbital biomaterials surgically explanted for recalcitrant infection. Methods: A search of the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine microbiology laboratory electronic database was conducted from 1980 to 2010. Culture results were analyzed from submitted periorbital biomaterials explanted for nonresolving infections or exposure. Random select samples cultured during the study were sent for electron microscopy. Results: Twenty-one explanted biomaterials were identified from 18 patients. Five orbital plate implants included 2 made of nylon, 1 of porous polyethylene, 1 of silicone, and 1 metallic. Of 4 anophthalmic socket sphere implants, 2 were silicone, 1 was porous polyethylene, and 1 was poly-2-hydroxyethyl methacrylate. Lacrimal intubation devices included 10 silicone stents and 2 pyrex glass Jones tubes. All biomaterials were culture positive with 40 total isolates identified. The most common organisms overall were Mycobacterium chelonae (N = 9), Staphylococcus aureus (N = 8), and Pseudomonas aeruginosa (N = 3). One hundred percent of orbital spheres had Gram-positive organisms, 90% of lacrimal silicone stents grew atypical mycobacterium, and 60% of orbital plates were culture positive for yeast species. Mixed organism growth was documented on 58% of the specimens. Ten of 12 implants (83%) examined with electron microscopy exhibited organisms encased in glycocalyx, suggestive of biofilm. Conclusions: A diverse array of microorganisms can colonize biomaterials implanted within the orbit and lacrimal drainage system. The authors’ study showed that the majority of infected periocular and orbital alloplastic implants display biofilm when studied with electron microscopy (83%). The cultured organism type depended on the implant location and composition. Most infected silicone lacrimal stents grew atypical mycobacterium, whereas infected orbital fracture repair plates demonstrated yeast species. Biofilms are known to be antibiotic resistant, explaining the need to explant most infected alloplastic implants. Further research concerning treatment of biofilms may prevent explantation and improve surgical outcomes. (Ophthal Plast Reconstr Surg 2013;29:376–381) T he expanding availability of implantable biomaterials has increased the use of synthetic material in oculofacial surgery. Biomaterials, such as acrylic, nylon, glass, silicone, hydroxyapatite, and porous polyethylene, provide the surgeon with an expanding armamentarium of surgical tools for treating orbital and periocular disease. They also may provide microorganisms with an immune-privileged, abiotic surface for growth. Recalcitrant infections associated with implants have been described in almost every part of the body where they have been used. The presence of biofilms on implants in ophthalmology has been documented on corneal sutures, punctal plugs, lacrimal intubation devices, scleral buckles, and intraocular lenses. 1–7