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The aim of the study was to investigate the effect of intravenous infusions of adenosine 5′-triphosphate (ATP) on nutritional status and survival in preterminal cancer patients. Ninety-nine preterminal cancer patients (estimated life expectancy 1–6 months) with mixed tumor types were randomly allocated to receive either intravenous ATP weekly (8–10 h/week, maximum 50 μg/kg/min) for 8 weeks, or no ATP (control group). Nutritional status parameters were assessed until 8 weeks, and analyzed by repeated-measures analysis of covariance. Cox proportional hazards models were fitted to assess the effect of ATP on short-term (0–8 weeks) and long-term (0–6 months) survival. Fifty-one patients were randomized to ATP and 48 to the control group. Results showed a significant favorable effect of ATP on triceps skin fold thickness [between-group difference per 8 weeks 1.76 mm, 95% confidence interval (CI): 0.48–3.12 mm; P = 0.009] and on short-term survival [0–8 weeks hazard ratio (HR): 0.40, 95% CI: 0.17–0.95; P = 0.037]. In weight-stable patients and in lung cancer patients, long-term survival (0–6 months) was also significantly better in ATP-treated patients (weight-stable patients HR: 0.40, 95% CI: 0.19–0.83; P = 0.014; patients with lung cancer: HR: 0.35, 95% CI: 0.14–0.88; P = 0.025). In conclusion, in this population of preterminal cancer patients, ATP infusions, at the dose and schedule studied, had a favorable effect on triceps skin fold thickness and survival, especially in weight-stable patients and patients with lung cancer. Larger studies are warranted to confirm these findings and to further define the effect of ATP on tumor growth and survival.