Background: Antibiotics provide only modest benefit in treating sore throat, although effectiveness increases in participants with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. Objectives: We assessed the comparative efficacy of different antibiotics on clinical outcomes, relapse, complications and adverse events in GABHS tonsillopharyngitis. Search methods: We searched The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 4, 2010) and EMBASE (1974 to August 2010). Selection criteria: Randomised, double-blind trials comparing different antibiotics reporting at least one of the following: clinical cure, clinical relapse, complications, adverse events. Data collection and analysis: Two authors independently screened trials for inclusion and extracted data. Main results: Seventeen trials (5352 participants) were included; 16 compared with penicillin (six with cephalosporins, six with macrolides, three with carbacephem and one with sulfonamides), one trial compared clindamycin and ampicillin. Randomisation reporting, allocation concealment and blinding were poor. There was no difference in symptom resolution between cephalosporins and penicillin (intention-to-treat (ITT) analysis; N = 5; n = 2018; odds ratio for absence of resolution of symptoms (OR) 0.79, 95% confidence interval (CI) 0.55 to 1.12). Clinical relapse was lower with cephalosporins (N = 4; n = 1386; OR 0.55, 95% CI 0.31 to 0.99); overall number needed to treat to benefit (NNTB) 50), but found only in adults (OR 0.42, 95% CI 0.20 to 0.88; NNTB 33). There were no differences between macrolides and penicillin. Carbacephem showed better symptom resolution post-treatment (N = 3; n = 795; OR 0.70, 95% CI 0.49 to 0.99; NNTB 14), but only in children (N = 2; n = 233; OR 0.57, 95% CI 0.33 to 0.99; NNTB 8.3). Children experienced more adverse events with macrolides (N = 1, n = 489; OR 2.33; 95% CI 1.06 to 5.15). Authors' conclusions: Evidence is insufficient for clinically meaningful differences between antibiotics for GABHS tonsillopharyngitis. Limited evidence in adults suggests cephalosporins are more effective than penicillin for relapse, but the NNTB is high. Limited evidence in children suggests carbacephem is more effective for symptom resolution. Data on complications are too scarce to draw conclusions. Based on these results and considering the low cost and absence of resistance, penicillin can still be recommended as first choice. Plain Language Summary: Different antibiotics for group A streptococcal pharyngitis Pharyngitis or tonsillitis, a throat infection that usually presents with a sore throat, is a common upper respiratory tract infection. Most sore throats are caused by viruses, but sometimes bacteria are involved. Many people carry bacteria in their throat without becoming ill. However, sometimes a bacterial throat infection can occur. Infection with a specific type of bacteria, group A beta-haemolytic streptococci (GABHS) is linked to serious complications such as acute rheumatic fever or kidney disease (post-streptococcal glomerulonephritis). In order to prevent these complications antibiotics are often prescribed to treat patients presenting to their doctor with a sore throat. A previous Cochrane review found that there is only a modest benefit of antibiotics for treating an acute sore throat, even if group A beta-haemolytic streptococci (GABHS) are present. Most throat infections, even with bacteria, are self-limiting and the risk of complications is extremely low in most populations studied (in low-income countries). However, sometimes antibiotics may be indicated. We found 17 trials with a total of 5352 participants that studied the effects of different classes of antibiotics on resolution of symptoms in patients with a sore throat and a positive culture for GABHS. Our review found that the effects of these antibiotics are very similar. All antibiotics studied also cause undesired side effects (such as nausea and vomiting, rash), but there was no strong evidence for meaningful differences between the antibiotics. The studies did not report on long-term complications and therefore it is unclear if any class of antibiotics is better in preventing these serious but rare complications. As all the identified studies were carried out in populations in high-income countries with a low risk of streptococcal complications, there is a need for trials in populations where this risk is still very high (low-income countries and Aboriginal communities). Penicillin has been used for a very long time but resistance of the GABHS to penicillin has never been reported. Also, penicillin is a cheap antibiotic. Our review therefore supports the use of penicillin as a first choice antibiotic in patients with acute throat infections caused by GABHS.