Background <p>Chronic postoperative pain is a&#xa0;common and often insufficiently treated complication that is closely linked with depressive and anxiety symptoms.</p> Objective <p>To investigate whether transcutaneous auricular vagus nerve stimulation (taVNS) reduces postoperative pain and if depressive or anxiety symptoms modulate the treatment effects.</p> Methods <p>In a&#xa0;three-arm, double-blind, randomized controlled trial, 44&#xa0;patients undergoing joint replacement surgery were allocated to an intervention group (<i>n</i> = 15), sham group (<i>n</i> = 17), or treatment as usual (TAU) control group (<i>n</i> = 12). Assessments were conducted at hospital admission (T₀) and before discharge (T₁) using the Short-Form McGill Pain Questionnaire (SF-MPQ), the Patient Health Questionnaire‑9 (PHQ-9) and the Generalized Anxiety Disorder 7 (GAD-7). Data were analyzed using mixed-design ANOVA and linear mixed-effects regression models with a&#xa0;Bonferroni correction.</p> Results <p>There were no significant main or interaction effects of group, time, or group × time on pain intensity (F(2,18) = 0.04, <i>p</i> = 0.959, η2 = 0.003; F(1,18) = 0.89, <i>p</i> = 0.358, η2 = 0.015). The PHQ‑9 scores showed trends for group and time effects (F(2,21) = 5.96, <i>p</i> = 0.009, η2 = 0.322; F(1,21) = 5.06, <i>p</i> = 0.035, η2 = 0.038). The GAD‑7 did not reveal significant effects. Moderation analyses did not indicate any significant effects of depressive or anxiety symptoms on pain change and combined moderation was not significant either.</p> Conclusion <p>In the present study, taVNS did not reduce postoperative pain and showed no moderating effects of depression or anxiety. Standardization of stimulation parameters, inclusion of psychological and somatic comorbidities and longer high-frequency follow-up periods are needed for future studies.</p> Graphic abstract <p></p>