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Purpose To investigate the effect of local usage of prilocaine and its combination with tramadol on the pain and anxiety levels of patients during nasal packing removal. Methods A total of 117 patients who were treated with the Merocel nasal packing after septoplasty were included in the study. Patients whose Merocel nasal packings infiltrated with prilocaine (P group), prilocaine combined with tramadol 1 mg/kg (P + T1 group), prilocaine combined with tramadol 2 mg/kg (P + T2 group), or normal saline solution (Control group) before nasal packing removal were compared for their pain, sedation, and anxiety related to this removal procedure. The visual analog scale (VAS), Ramsay sedation scale (RSS), and State-Trait Anxiety Inventory (STAI) scale were assessed to evaluate the pain, sedation, and anxiety levels of the patients. Results Groups were found similar according to sex, age, and preoperative STAI scores. The VAS score was significantly lower in P, P + T1, and P + T2 than control group during nasal packing removal (p < 0.001, p < 0.001, and p < 0.001, respectively). However, state anxiety inventory (STAI-S) and RSS were found significantly improved only in P + T1 and P + T2 (STAI-S: p = 0.032, RSS: p = 0.002, STAI-S: p = 0.000, RSS: p < 0.001, respectively). In the comparison of P + T1 and P + T2, no significant difference was found in VAS, RSS, and STAI-S (p = 0.604, p = 0.154, and p = 0.264, respectively). Conclusion The combined infiltration of prilocaine and tramadol 1 mg/kg into the nasal packing is effective in reducing the pain and anxiety of patients during nasal packing removal.