Acute diffuse otitis externa is an acute inflammatory condition of the external auditory canal commonly associated with otalgia and ear canal oedema. Standard management includes aural toilet, pain control, and topical antimicrobial therapy, which may be administered using ear tampons with or without corticosteroids. This study aimed to compare the effectiveness of single-antibiotic ear tampons versus antibiotic–steroid combination ear tampons in reducing pain and ear canal oedema in patients with acute diffuse otitis externa. This double-blind randomized controlled clinical trial analyzed 40 patients with acute diffuse otitis externa who completed follow-up and were assigned to receive either single-antibiotic ear tampons or antibiotic–steroid combination ear tampons. Pain intensity was assessed using the Visual Analog Scale, and ear canal oedema was evaluated using the Brighton scale at baseline and on days 1, 3, and 5 after tampon insertion. Longitudinal analysis was performed using repeated-measures models.  Both treatment groups demonstrated significant improvement in pain and oedema over time. However, longitudinal analysis showed that the antibiotic–steroid combination group experienced a significantly faster reduction in pain than the single-antibiotic group, whereas the trajectory of oedema improvement did not differ significantly between groups. Multivariable longitudinal analysis confirmed that treatment type and baseline pain severity were associated with pain outcome, while baseline oedema severity was strongly associated with oedema outcome. Both treatment regimens were effective over time, but antibiotic–steroid ear tampons provided faster pain relief, while oedema improvement remained comparable between groups.