Background and Objectives: Due to the steadily progressive development of resistance to the drugs used for treatment, Neisseria gonorrhoeae remains a medical concern. Trospectomycin sulfate is a 6’ propyl analogue of spectinomycin with potent activity against penicillin sensitive and resistant strains of N. gonorrhoeae. Goal of this Study: To compare the efficacy of 250 mg trospectomycin sulfate IM versus 250 mg ceftriaxone IM for single dose therapy for men and women with uncomplicated gonorrhea. Study Design: Dual-center, randomized comparative trial. Results: Among evaluable male patients with urethral gonorrhea, 36 of 40 (90%, 95% confidence interval [95%CI] 76%-97%) who were treated with trospectomycin sulfate were cured, and 22 of 22 patients (100%, [85%-100%]) treated with ceftriaxone were cured. Among evaluable female patients with cervical gonorrhea all were cured following trospectomycin sulfate (23 of 23) and following ceftriaxone therapy (13 of 13). The cure rates for pharyngeal gonorrhea were 67% (8 of 12 patients, 35%-90%) for trospectomycin sulfate therapy, and 100% (2 of 2) with ceftriaxone therapy. Conclusions: Trospectomycin sulfate, 250 mg IM, is effective, and well tolerated. However, for treatment of uncomplicated genital and pharyngeal gonorrhea, it is not as reliable for therapy as other recommended regimens. © 1994 American Sexually Transmitted Diseases Association.