The antibacterial activities of camphorated paramonochlorophenol, chlorhexidine, and calcium hydroxide were compared using a clinical and laboratory evaluation. In the clinical experiment, root canals that yielded positive cultures a week after complete chemomechanical preparation and camphorated paramonochlorophenol dressing were medicated with one of the three substances tested. Postmedication samples were taken from the canal 1 week later. In the laboratory experiment, the agar diffusion test was used to evaluate the inhibitory activity of the medicaments against bacteria commonly found in endodontic infections. The results of the clinical evaluation showed that all medicaments were effective in reducing or eliminating the endodontic microbiota, as demonstrated by the incidence of negative cultures. There was no statistically significant difference among the medicaments tested. In the laboratory evaluation, camphorated paramonochlorophenol showed the largest zones of bacterial inhibition against all bacterial strains tested.