Backgrounds Many patients with gastric cancer relapse during or early after adjuvant chemotherapy. The standard treatment for early relapse patients is a second-line chemotherapy (SLC) based on irinotecan, taxanes, or a platinum-based chemotherapy. The platinum-containing biweekly irinotecan plus cisplatin (IRI/CDDP) combination was assumed to be promising in several reports of clinical trials as SLC. TRICS trial, a randomized phase III study of IRI/CDDP vs. IRI in platinum-naïve gastric cancers refractory to S-1 monotherapy, revealed that both irinotecan-based chemotherapies were effective and well tolerated. Methods This study analyzed 108 patients in the TRICS trial who experienced early relapse. Patients receiving IRI/CDDP (IRI, 60 mg/m 2 ; CDDP, 30 mg/m 2 , q2w) versus IRI (150 mg/m 2 , q2w) were compared regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. Results The OS was 14.0 (95% confidence interval CI: 11.0–21.2) and 14.0 (95% CI: 10.7–16.5) months for IRI/CDDP and IRI, respectively (hazard ratio HR: 0.782; 95% CI: 0.515–1.188, P  = 0.249). No significant differences were observed for PFS (5.0 vs. 4.5 months, respectively; HR: 0.802; 95% CI: 0.543–1.185, P  = 0.268) or ORR (19.6% 95% CI: 9.4–33.9% vs. 23.3% 95% CI: 11.8–38.6%, respectively). The incidence of grade 3–4 anemia was higher for IRI/CDDP than for IRI (20% vs. 0%, respectively; P  = 0.0006). Conclusion Our study showed no significant survival differences between IRI/CDDP and IRI in platinum-naïve patients who relapsed during or within 6 months after S-1 adjuvant therapy; therefore, IRI may be a good option in this population. Clinical trial information UMIN 000002571.