Objectives: Tonsillectomy (TE) and tonsillotomy (TO) due to recurrent episodes of acute tonsillitis (RAT) belong to the most frequent surgical procedures. However, an adequate objective marker predicting the outcome of TE/TO preoperatively is missing. Methods: Patients with RAT who underwent TE/TO (n = 31) were included in this pilot study. A panel of cytokines and chemokines in serum and saliva were determined preoperatively. Health-related quality of life was assessed pre- and postoperatively by the Tonsillectomy Outcome Inventory-14. Results: Health-related quality of life improved significantly after surgery. Increased serum levels of interleukin-8 (IL-8) and interferon gamma (IFN-γ) are associated with a less successful outcome. No correlation between the number of acute tonsillitis episodes and the health-related quality of life after TE or TO could be observed. Conclusions: Tonsillectomy and TO improve health-related quality of life independently from the number of past acute tonsillitis episodes. Interleukin-8 and IFN-γ in serum may serve as promising markers, predicting the benefit of TE or TO for patients preoperatively.