Ceftriaxone is the current first-line treatment for gonorrhoea; however, antibiotic resistance is emerging and new approaches are needed. The G-ToG study was a multicentre, parallel-group, randomized noninferiority trial that compared treatment with gentamicin with ceftriaxone for gonorrhoea at 14 sexual health clinics in England. Patients received either 240 mg of gentamicin or 500 mg of ceftriaxone as a single intramuscular injection plus 1 g of oral azithromycin. In total, 720 participants (81% male) were randomized, 358 in the gentamicin group and 362 in the ceftriaxone group. Clearance of genital infection was similar in the two groups (94% in the gentamicin group and 98% in the ceftriaxone group), but clearance of pharyngeal infection and rectal infection was lower in the gentamicin group (80% versus 96% and 90% versus 98%, respectively). Overall, the trial was unable to demonstrate noninferiority of gentamicin compared with ceftriaxone in the clearance of gonorrhoea at all infected sites. Furthermore, gentamicin was associated with more severe pain at the injection site and higher costs.