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Objectives: To determine the effect of guided imagery (GI) on functional outcomes of total knee replacement (TKR), explore psychological and neuroimmune mediators, and assess feasibility of study implementation. Design: Investigator-blinded, randomized, placebo-controlled pilot study. Settings: Hospital, surgeon's office, participant's home. Participants: 82 persons undergoing TKR. Interventions: Audiorecordings of TKR-specific GI scripts or placebo-control audiorecordings of audiobook segments. Outcome measures: Gait velocity and Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function scale.Results: Outcomes for 58 participants (29 receiving GI and 29 controls) were analyzed at 6 months after surgery. The most frequent reason for noncompletion was protocol-driven exclusion at 6 months for having the contralateral knee replaced before the study endpoint (n = 15). With imaging ability as a moderator, gait velocity, but not WOMAC Function score, was significantly improved at 6 months in the GI group. Participants in the GI group, but not the control group, had lower WOMAC Pain scores at 3 weeks after surgery than at baseline. Hair cortisol concentration was significantly lower at 6 months after surgery than at baseline in the GI group but not the control group. GI group participants had lower treatment adherence but greater treatment credibility than the control group. Conclusion: Randomized controlled trials of GI in the TKR population are feasible, but inclusion/exclusion criteria influence attrition. Further studies are needed to elaborate this study's findings, which suggest that guided imagery improves objective, but not patient-reported, outcomes of TKR. Hair cortisol concentration results suggest that engagement in a time-limited guided imagery intervention may contribute to stress reduction even after the intervention is terminated. Further investigation into optimal content and dosing of GI is needed.

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