Background. We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Methods. This prospective study included patients with coronavirus disease 2019 (COVID-19) with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quant. IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serol. platforms. Positivity of reverse transcription-polymerase chain reaction or vaccination was considered as the reference standard Results. A total of 239 individuals were included (152 convalescent, 54 vaccinated, and 33 uninfected unvaccinated). Overall sensitivity, specificity, and pos.- and neg.-predictive values (95% confidence interval) of the IGRA were 81.1% (74.9-86%), 90.9% (74.5-97.6%), 98.2% (94.5-99.5%), and 43.5% (31.8-55.9%), resp. All vaccinated SARS-CoV-2-naive subjects had pos. IGRA at 3 mo. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3 mo and the worst in those with mild disease at 12 mo. The greatest contribution of IGRA to serol. tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). Conclusions. The IGRA was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients, the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clin. value to serol. in patients with mild infections.