Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P = 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol. Methods: Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines. Results: Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm. Conclusions: Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372.