The effectiveness of traditional endodontic intracanal medications in reducing bacterial numbers and preventing acute flare-ups and pain continues to be questioned. In the present study, a new local delivery device was developed that releases a substantive dose of clindamycin into root canals. Clindamycin-impregnated ethylene vinyl acetate (EVA) fibers were produced, and the sensitivity of common endodontic microbes to the fibers were established. An in vitro model was developed to persistently infect 32 extracted human teeth with endodontic pathogens to test the efficacy of the clindamycin/EVA fibers in reducing the number of colony-forming units. The clindamycin/EVA fibers were shown to be effective in reducing growth of common endodontic microbes on blood agar plates, and in significantly reducing growth of Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus intermedius in extracted human teeth, thus indicating merit in further exploring the potential of these fibers as intracanal medications.