Background: Neoadjuvant immune checkpoint inhibitors (ICIs) are being explored in resectable non-small cell lung cancer (NSCLC). Here, we studied the composition and changes in the T cell repertoire in a cohort of NSCLC patients (n = 44) treated with neoadjuvant nivolumab (N) alone or in combination with ipilimumab (NI) followed by surgery (NEOSTAR trial). Methods: Sequencing of the variable CDR3β chain of the T cell receptor (TCR) involved in antigen binding was performed in pre-treatment and surgical tumors, matched adjacent uninvolved lung specimens, as well as paired longitudinal blood at baseline, prior to each dose of therapy, prior to surgery, and within 8 weeks post-surgery. T cell repertoire density, diversity, and clonality (reactivity) were evaluated in addition to tumor PD-L1 expression pre- and post-neoadjuvant treatment. Results: Median T cell diversity in the blood post-therapy was 3.3-fold higher in NI- compared to N-treated patients (40,993 [NI, n = 3] vs 12,177 [N, n = 4] unique TCR rearrangements, n.s.). However, median T cell clonality in the blood was 3.5-fold higher in N- than NI-treated patients post-therapy (0.093 [N, n = 4] vs 0.026 [NI, n = 3], n.s.). Median clonality was 3.8-fold higher in the tumor post-therapy in patients receiving NI than in those receiving N (0.076 [NI, n = 7] vs 0.020 [N, n = 5], n.s.). Interestingly, diversity in the blood at baseline and in the tumor post-therapy were positively correlated ([n = 7], r = 0.82; p = 0.023), which may reflect an influx of cells from the periphery following ICIs. Importantly, higher baseline T cell clonality in the blood was associated with a lower % of viable tumor at time of surgery in both treatment arms ([n = 7], r = -0.77; p = 0.04). Conclusions: Our study is the first to assess the TCR repertoire in NSCLC patients treated with combination neoadjuvant NI and highlights potential mechanistic differences compared to N alone. Neoadjuvant NI is associated with higher clonality in tumors and lower clonality in blood post-therapy, suggesting increased T cell trafficking into the tumor. Finally, lower pre-treatment clonality in the periphery was correlated with higher % viable tumor post-neoadjuvant ICIs. Clinical trial information: NCT03158129