A randomized, single-blind, controlled study comparing the efficacy of an ointment containing two antibiotics, one containing one antibiotic plus hydrocortisone, and no treatment in reducing secondary infections in patients with patent Guinea worm was undertaken in the northern region of Ghana. Seventy seven patients were included. Time to complete healing was significantly shorter in the treatment groups compared with the controls (P = 0.044 and P = 0.003, respectively). Secondary infections occurred more often in the controls (P = 0.00014). Ointments containing antibiotics are recommended for application at the early stage of patent Guinea worm infection.