Purpose. To assess the in vitro susceptibility of ocular bacterial isolates from North and South America to antiinfectives that are commonly used in the treatment of external ocular infection. Methods. Ocular isolates (n = 1,291) from 12 laboratories in the United States, Canada, Mexico, and Argentina were tested for their susceptibility to ofloxacin, ciprofloxacin, norfloxacin, gentamicin, tobramycin, chloramphenicol, tetracycline, and erythromycin using both disk-diffusion and broth-dilution methods. Results. When the results from disk-diffusion and broth-dilution testing were combined, the relative overall in vitro efficacy was (in decreasing order): ofloxacin, ciprofloxacin, norfloxacin, gentamicin, chloramphenicol, tobramycin, tetracycline, and erythromycin. Against grampositive organisms it was: ofloxacin, ciprofloxacin equivalent to chloramphenicol, norfloxacin, tetracycline, gentamicin, and erythromycin equivalent to tobramycin. Against gram-negative organisms it was: ofloxacin equivalent to ciprofloxacin and norfloxacin, gentamicin, tobramycin, chloramphenicol, and tetracycline comparable to erythromycin. Conclusions. The fluoroquinolones ofloxacin, ciprofloxacin, and norfloxacin had higher overall in vitro efficacy than the other antibiotics tested. Of the fluoroquinolones, ofloxacin had the highest in vitro efficacy against gram-positive organisms. All three fluoroquinolones were equivalent in efficacy against gram-negative organisms.