Background. Chronic otorrhoea is difficult to treat, with treatment in South Africa (SA) being protocol driven and generally initiated at the primary healthcare level. There is a lack of local studies that focus on the bacteriology and antimicrobial sensitivities of chronic otorrhoea, which underpins the management advice offered.Aims. To determine the microbiological profile and antimicrobial susceptibility of patients with chronic otorrhoea and the validity of the Department of Health’s (DoH) current guideline.Methods. We conducted a prospective study at Groote Schuur Hospital from 2005 to 2009. We included patients with chronic otorrhoea classified as either otitis media or otitis externa, according to our definitions. Pus swabs were taken, from which microorganisms were cultured and tested for antimicrobial susceptibility.Results. Of 79 patients with otorrhoea, 50 had otitis media, 21 had otitis externa and the condition was not determined in 8 patients. The most common organism isolated with otitis media was Proteus mirabilis (18/50; 36%) and with otitis externa, Pseudomonas aeruginosa (7/21; 33%). Otorrhoea had a different microbial spectrum compared with international reports, with methicillin-resistant Staphylococcus aureus infection in a single patient. The organisms isolated were susceptible mainly to fluoroquinolones (96%) and aminoglycosides (81%).Conclusion. Amoxicillin is a poor choice of antibiotic due to its low sensitivity, which calls into question the current DoH guideline for otorrhoea. Antimicrobial treatment protocols should be based on local data and be revisited from time to time. This study suggests that, should first-line treatment fail, an antibiotic with Gram-negative cover, e.g. a topical fluoroquinolone, should be considered.