One hundred fourteen heterosexual men with acute nongonococcal urethritis (NGU) and 64 patients without NGU were studied. We determined that Chlamydia trachomatis and Mycoplasma genitalium were strongly associated with acute NGU after controlling, by means of multivariate analysis, for age, race, sexual lifestyle, and coinfection (odds ratio [OR], 13.0, 95% confidence interval [CI], 2.6-64.5; and OR, 17.9, 95% CI, 2.0-160, respectively). Eighty-six men with acute NGU reattended at least once 10-92 days after treatment; 59 (69%) of these 86 men had urethritis. Seven men had M. genitalium detected during 10-92 days of follow-up, and all had urethritis. Ureaplasmas were not associated with acute NGU in multivariate analysis, but their detection was associated with the presence of urethritis during follow-up (P=.014). Ureaplasmas or M. genitalium were associated with both chronic NGU, which was defined as urethritis that occurred 30-92 days after the commencement of treatment (P=.028), and chronic NGU with symptoms or signs (P=.005).