Background Peritonsillar abscess is a common clinical problem. Management involves drainage of the abscess and administration of antibiotics. The choice of antibiotic is related to the polymicrobial growth of aspirate cultures, leading to prescriptions of co-amoxiclav, or metronidazole in addition to phenoxymethylpenicillin. However there is little evidence to support this. Objectives The aim of this review was to assess clinical effectiveness of phenoxymethylpenicillin vs phenoxymethylpenicillin plus anaerobic cover in the management of peritonsillar abscess. Design/Setting A systematic review of literature and clinical trial databases in accordance with the PRISMA 2020 statement. Studies were screened for eligibility by two independent reviewers. Main outcome measure Three studies were included, two comparing oral penicillin to oral penicillin plus metronidazole, one comparing IM/oral penicillin to IM/oral sulbactam-ampicillin. Clinical outcomes were assessed in all, including recurrence rate, symptom improvement and duration of pyrexia. Results There was no significant difference in any clinical outcome across all studies between the two groups. One study found a significant increase in diarrhoea and vomiting as a side effect in the group receiving metronidazole plus penicillin compared to penicillin alone (p=0.01). Conclusion On reviewing the literature, no significant clinical benefit has been demonstrated in the addition of either metronidazole or more broad-spectrum antibiotic cover compared to oral penicillin monotherapy for peritonsillar abscess when combined with incision and drainage protocols. Moreover, unnecessary broad-spectrum antibiotics contribute to increased side effects, costs, and antimicrobial resistance.