Background/Objectives: Biodegradable polymers like poly(L-lactide-co-D,L-lactide) (PLDLLA) and polyetheretherketone (PEEK) are clinically used as temporary orthopedic implants. Although polylactic acid (PLA) has comparable mechanical properties, its 3D-printed form lacks clinical validation. This study aimed to assess whether 3D-printed PLA exhibits biocompatibility, structural stability, and bone integration similar to PLDLLA and PEEK. Methods: The study consisted of in vitro and in vivo phases. In vitro, 3D-printed PLA screws were immersed in simulated body fluid (SBF) to evaluate structural integrity and degradation. In vivo, PLA, PLDLLA, and PEEK screws were implanted into porcine femurs and analysed by computed tomography and histological examination to assess osseointegration and implant stability. Results: In vitro, PLA maintained structural integrity in SBF without premature degradation. In vivo, PLA exhibited progressive bone formation and osteointegration by 3–4 months, though neovascularization was limited. PLDLLA showed direct cortical bone integration with mild inflammation, while PEEK induced fibrointegration without osteoid formation. Conclusions: 3D-printed PLA demonstrated biocompatibility and bone integration comparable to PLDLLA and a more favorable osteogenic response than PEEK. These findings support its potential as a biodegradable orthopedic implant, though further studies are needed to confirm long-term clinical safety and efficacy.