OBJECTIVES: According to the four-year follow-up results of an open, randomized, phase II study, this patient-based cost-effectiveness analysis compares mFOLFIRI (irinotecan, 5-fluorouracil and leucovorin，IRI arm) with mFOLFOX7 (oxaliplatin, 5-fluorouracil and leucovorin，OXA arm) as first-line treatments in patients with locally advanced gastric adenocarcinoma(GC). METHODS: A Markov model was created based on previous results reported on 2016 Gastrointestinal Cancers Symposium to evaluate mFOLFIRI and mFOLFOX7 for advanced GC. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs) were examined as the primary outcomes. RESULTS: For evaluable 128 patients, treatment efficacy was 0.59 QALYs for IRI arm and 0.70 QALYs for OXA arm, with a total cost of $13,861.34 for IRI arm and $14,127.30 for OXA arm. Hence, OXA arm had lower cost per QALY compared with IRI arm contributing to an ICER of $2,417.82 per QALY for OXA arm, which was below the threshold of 3× per capita GDP of China. For subgroup analysis of those receiving mFOLFIRI followed by mFOLFOX7 (IRI arm) and the reverse (OXA arm), OXA arm gained 0.44 more QALYs compared with IRI arm with a total cost of $28,890.09 for IRI arm and $31,147.30 for OXA arm. However, the cost per QALY was also lower for OXA arm compared with IRI arm, leading to an ICER of $5,129.55 per QALY for OXA arm, which was also below the threshold. CONCLUSIONS: Both mFOLFIRI and mFOLFOX7 are affordable for the first-line treatments of advanced GC, but mFOLFOX7 is more cost-effective. Additionally, mFOLFOX7 followed by mFOLFIRI was an optimal sequence with more effectiveness and acceptable cost.