Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. The probiotic Streptococcus salivarius has been shown to be effective in reducing the frequency of recurrent pharyngeal infections in children and adult populations. However, probiotics have not yet been evaluated in the treatment of acute pharyngotonsillitis in adults. We aimed to examine whether the addition of S. salivarius probiotics to the routine therapy of acute pharyngotonsillitis in adult patients may shorten disease duration and reduce symptom severity. This study was a prospective, randomized, placebo-controlled, double-blinded study comparing treatment with probiotics to placebo in addition to antibiotics in patients who were hospitalized with severe pharyngotonsillitis. Laboratory results, pain levels, body temperature, and daily volume of fluids consumed were recorded for both groups. Sixty participants were recruited, 30 for each group. No statistically significant differences between the two groups were observed regarding any of the major clinical and laboratory parameters examined. Supplement probiotic treatment with S. salivarius in patients with acute pharyngotonsillitis treated with penicillin is ineffective in relation to the parameters examined in this study and we cannot, therefore, recommend the use of S. salivarius during active pharyngotonsillar infection treated with penicillin.