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Introduction: Cytomegalovirus (CMV) causes significant morbidity in solid organ transplant recipients (SOTR). Measuring cell-mediated immunity (CMI) may inform the risk of CMV infection after antiviral prophylaxis and predict relapse after CMV treatment., Methods: We serially assessed CMV CMI using the QuantiFERON-CMV assay (QF-CMV; Qiagen, Germantown, MD) in two cohorts of SOTRs: during valganciclovir prophylaxis and during treatment of CMV viremia. Results of CMI were correlated with post-prophylaxis CMV infection and post-treatment relapse, respectively., Results: Only one (4.2%) of 24 CMV D+/R- patients demonstrated positive QF-CMV by the end of valganciclovir prophylaxis. Four (16.6%) patients developed post-prophylaxis CMV infection; all four had undetectable QF-CMV at end of prophylaxis. Among 20 patients treated for CMV infection, 18 (90%) developed QF-CMV levels >.2 IU/mL by end of antiviral treatment and none developed CMV relapse. In contrast, the single patient who relapsed after completing treatment had a CMV CMI <.2 IU/ml (p = .0036)., Conclusion: Since CMV D+/R- SOTRs are unlikely to develop adequate CMV CMI while receiving valganciclovir prophylaxis, the utility of CMV CMI monitoring for risk stratification during time of prophylaxis had limited value. Conversely, CMV CMI testing may be a useful marker of the risk of CMV relapse after antiviral treatment., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)