We conducted a systematic review and meta-analysis of ceftriaxone for treatment of uncomplicated gonorrhoea compared with four other antibiotics. Thirteen randomized controlled trials (RCTs) totalling treatment of 2557 patients with uncomplicated gonorrhoea were included. Statistically significant differences were observed in side-effects, which were increased after ceftriaxone 250 mg versus cefotaxime 500 mg (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.14-3.08). Cure rates of ceftriaxone 250 mg were significantly better than cefixime 400 mg (OR 1.77; 95% CI 1.11-2.80) as was ceftriaxone 125 mg versus spectinomycin 2 g (OR 3.44; 95% CI 1.08-10.90). There was no statistically significant difference between ceftriaxone 250 mg and cefixime 800 mg in cure rates (OR 1.39; 95% CI 0.92-2.10) or adverse effects (OR 1.29, 95% CI 0.58-2.84) for treating uncomplicated gonorrhoea. The cure rate after ceftriaxone 250 mg was not significantly different from that after spectinomycin 2 g (OR 1.96; 95% CI 1.00-3.87). In conclusion, this meta-analysis revealed that 250 mg ceftriaxone had a higher efficacy than 400 mg cefixime for uncomplicated gonorrhoea. Also, ceftriaxone 125 mg is a better choice than spectinomycin 2 g for patients with uncomplicated gonorrhoea, but ceftriaxone had higher side-effect rates than cefotaxime. In the current era further randomized controlled clinical trials of ceftriaxone for uncomplicated gonorrhoea are warranted.