Neisseria gonorrhoeae infection remains relatively common in the United States, representing a public health challenge. Ligase chain reaction (LCR) is both highly sensitive and specific for the detection of N. gonorrhoeae in urine and patient-obtained vaginal swab specimens. Because of the LCR test's exquisite sensitivity, it may potentially detect DNA from nonviable organisms following effective therapy, leading to false-positive test results and unnecessary additional treatment. The purpose of the present study was to determine the duration that gonococcal DNA is detectable by LCR following therapy for uncomplicated gonococcal infection. One hundred thirty men and women between the ages of 16 and 50 years presenting to a sexually transmitted disease clinic with urogenital gonorrhea were enrolled. After the standard history was taken and a genital examination was done, the patients were asked to submit either a urine specimen (men) or a urine specimen plus a self-obtained vaginal swab specimen (women) for N. gonorrhoeae testing by LCR at the initial visit and each day during the study period. At enrollment, patients were treated with single doses of ofloxacin, cefixime, or ceftriaxone. The median time to a negative urine LCR test result was 1 day for the men (mean, 1.6 ± 0.14 days) and 2 days for the women (mean, 1.7 ± 0.19 days). Among the women the clearance time was significantly longer for vaginal specimens (mean, 2.8 ± 0.30 days) than for urine specimens (mean, 1.7 ± 0.11 days). Irrespective of patient gender and specimen type, gonococcal DNA can be expected to be absent from urogenital specimens within 2 weeks following successful therapy.