From in vitro studies it is known that a plasma-treatment can enhance cell spreading. Similar effects can be observed after pretreatment of the surface with a protein coating, to mediate cell adhesion. The aim of the current study was to evaluate the in vivo effects of these surface modifications, in a three-month experiment in a goat model. We made silicone and poly-L-lactic acid implants with double-sided parallel micro-grooves (depth 1.0 microm, width 10.0 microm), a random surface roughness, or a smooth surface. Implants either received a radio-frequency glow discharge (RFGD) treatment, a fibronectin (Fn) pre-coating, or no pre-treatment. Subsequently, they were inserted into subcutaneous pockets created on the flanks of goats for 1, 3 or 12 weeks. Histological analysis showed that a fibrous tissue capsule had formed around all implants. Histomorphometrical analysis was performed on capsule thickness, capsule quality and the implant-tissue interface quality. Fn-treated surfaces showed a considerable early inflammatory reaction. Besides this, RFGD treatment or Fn pre-coating did not further influence any of the measured parameters. In conclusion, pre-treatment of polymer implant surfaces with Fn or RFGD treatment did not significantly influence tissue reaction around implants with micro-grooved, roughened or smooth surfaces.