A new series of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles (6a–h) were synthesized and evaluated by the disc diffusion method against Helicobacter pylori. Four compounds which exhibited strong anti-H. pylori activity at concentration of 8–32 lg/disc (average of inhibition zone>20 mm) were further tested against 20 clinical isolates of H. pylori at lower concentrations. The averages of inhibition zone diameters indicated that all selected compounds exhibit better anti-H. pylori activity profile against clinical isolates of H. pylori with respect to standard drug metronidazole. Compound 6c, containing the 3-chlorobenzylthio moiety, was the most potent compound tested.