Objective: To evaluate the synergistic activity of norfloxacin and metronidazole in vitro. Methods: Aerobic (n=36) and anaerobic (n=30) bacterial isolates were obtained from clinical samples collected from urine, stool, pus and blood of patients suffering from urinary tract infections, gangrene, diabetic foot, dental infections, liver abscess, breast abscess, puerperal sepsis and infected traumatic wounds. Antibiotic susceptibility to norfloxacin and metronidazole was determined by minimal inhibitory concentration (MIC). Results: Among the aerobic isolates studied, 6 showed complete synergistic effect to the combination of norfloxacin and metronidazole while 30 showed partial synergistic or additive effects. Among the anaerobic isolates studied, 19 showed complete synergy while 8 showed partial synergy. Only 2 isolates of Bacteroides fragilis and 1 isolate of Porphyromonas asaccharolytica did not show any synergy. Complete synergy is shown by isolates of Salmonella species and Escherichia coil causing diarrhoea, Proteus species and Escherichia coli causing gram negative septicemia and systemic infections like urinary tract infections, Clostridium welchii and Clostridium sporogenes causing gangrene and diabetic foot, Prevotella melaninogenica, Fusobacterium necrophorum and Porphyromonas asaccharolytica causing dental infections, Fusobacterium nucleatum causing liver abscess, Bacteroides fragilis causing liver abscess and breast abscess, Peptostreptococcus anaerobius causing puerperal sepsis and diabetic foot and Peptostreptococcus asaccharolyticus causing traumatic wounds. Conclusion: The combination of norfloxacin and metronidazole has synergistic action in vitro and may may be useful In the treatment of mixed infections.