The treatment of recurrent genital herpes typically involves daily doses of acyclovir for extended periods. Additive manufacturing is an intriguing technique for creating personalised drug delivery systems, which can enhance the effectiveness of treatments for various diseases. The vaginal route offers a viable alternative for the systemic administration of drugs with low oral bioavailability. In this study, we produced different grades of thermoplastic polyurethane (TPU) filaments through hot-melt extrusion, with acyclovir concentrations of 0%, 10%, and 20% by weight. We used fused filament fabrication to manufacture matrix-based devices, including intrauterine devices and intravaginal rings. Our results, obtained through SEM, FTIR, and DSC analyses, confirm the successful incorporation of acyclovir into the matrix. Thermal analysis reveals that the manufacturing process alters the organization of the TPU chains, resulting in a slight reduction in crystallinity. In our in-vitro tests, we observed an initial burst release on the first day, followed by sustained release at reduced rates for up to 145 days, demonstrating their potential for long-term applications. Additionally, cytotoxicity analysis suggests the excellent biocompatibility of the printed devices, and biological assays show a remarkable 99% reduction in HSV-1 replication. In summary, TPU printed devices offer a promising alternative for long-term genital herpes treatment, with the results obtained potentially contributing to the advancement of pharmaceutical manufacturing.