Tigemonam, an oral monobactam that exhibits beta-lactamase stability similar to that of aztreonam, was tested in vitro against 240 species of Enterobacteriaceae (50 Escherichia coli, 48 Klebsiella pneumoniae, 52 Enterobacter cloacae, 32 Proteus mirabilis, 22 Proteus indole-positive [Providencia sp.], 24 Serrada sp., and 12 Citrobacter sp. All strains were resistant to ampicillin and first-generation cephalosporins. In addition, 77.4% were resistant to amoxicillin plus clavulanic acid, 46.8% to cefuroxime, 23.3% to ceftriaxone, 22.2% to aztreonam, 46.9% to cotrimoxazole, and 0.9% to norfloxacin. Tigemonam at a concentration of 4 μg/mL or less inhibited 72.7% of the strains with minimum inhibitory concentrations ranging from 0.03 or less to more than 512 μg/mL. The highest intrinsic activity was observed against Proteus sp. Tigemonam proved to be a bactericidal antibiotic. Cross-resistance was chiefly observed with aztreonam and ceftriaxone. It is concluded that tigemonam should play an important role in the treatment of nosocomial infections that do not require parenteral therapy and in the treatment of multiresistant community-acquired infections.