OBJECTIVES To estimate the cost-effectiveness of nab-paclitaxel+gemcitabine (Npg) versus gemcitabine (Gem) alone for the first-line treatment of metastatic pancreatic cancer in Greece from a National Health System perspective METHODS A Markov model was developed, included several stages such as: “pre-progression on first-line treatment”, “pre-progression off first-line treatment”, “post progression”, “four weeks to death” and “death”. Data from the MPACT trial were used to estimate overall survival (Life-Years-(LYs)) and adverse events. The prices of drugs used in the model are publicly available for all hospitals in Greece. Cost assigned in each health state reflected: drugs, adverse events, monitoring, administration and palliative care. Utility values were obtained from the international literature to estimate Quality-Adjusted-Life-Years (QALYs). Costs and health gains were discounted at 3.5% per annum. A probabilistic sensitivity analysis was also conducted to construct confidence intervals (CI). RESULTS The mean number of QALYs was 0.71 (95%CI: 0.66–0.78) and 0.56 (95%CI: 0.52–0.60) for Npg and Gem, respectively, giving an incremental gain of  0.15 (95%CI: 0.08-0.25) QALYs in favour of Npg. The mean cost of therapy per patient was estimated at €15,628 (95%CI:€14,377- €17,027) and €8,284 (95%CI:€7,455-€9,112) for Npg and Gem, respectively. The incremental cost per LY gained with Npg was estimated at €37,007 and the incremental cost per QALY gained at €47,120. The probability for Npg to be cost-effective at a threshold three times the per capita income (€60,000 per QALY) was 82%. CONCLUSIONS The severity of pancreatic cancer, in combination with the limited number of effective treatments, results in a high level of unmet need.  If the societal willingness-to-pay threshold for an additional QALY is relatively higher for patients with short life expectancy or for diseases with a relatively higher burden, the combination of nab-paclitaxel+gemcitabine could be considered a cost-effective choice compared with gemcitabine alone in Greece.