Background: We evaluated the feasibility and tolerability of triple- versus double-drug chemotherapy in elderly patients with oesophagogastric cancer. Methods: Patients aged 65 years or older with locally advanced or metastatic oesophagogastric cancer were stratified and randomised to infusional 5-FU, leucovorin and oxaliplatin without (FLO) or with docetaxel 50 mg/m2 (FLOT) every 2 weeks. The study is registered at ClinicalTrials.gov, identifier NCT00737373. Findings: One hundred and forty three (FLO, 71; FLOT, 72) patients with a median age of 70 years were enrolled. The triple combination was associated with more treatment-related National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 adverse events (FLOT, 81.9%; FLO, 38.6%; P <.001) and more patients experiencing a ≥10-points deterioration of European Organization for Research and Treatment of Cancer Quality of Life (EORTC QoL) global health status scores (FLOT, 47.5%; FLO 20.5%; p =.011). The triple combination was associated with more alopecia (P <.001), neutropenia (P <.001), leukopenia (P <.001), diarrhoea (P =.006) and nausea (P =.029).). No differences were observed in treatment duration and discontinuation due to toxicity, cumulative doses or toxic deaths between arms. The triple combination improved response rates and progression-free survival in the locally advanced subgroup and in the subgroup of patients aged between 65 and 70 years but not in the metastatic group or in patients aged 70 years and older. Interpretation: The triple-drug chemotherapy was feasible in elderly patients with oesophagogastric cancer. However, toxicity was significantly increased and QoL deteriorated in a relevant proportion of patients. Funding: The study was partially funded by Sanofi-Aventis.