Effect sizes of efficacy of first-line treatments for (metastatic) pancreas cancer are constrained, underscoring the need for evaluations of the efficacy-to-cost relationship. We critically review economic evaluations of first-line chemotherapy regimens for pancreatic cancer since the 1997 introduction of gemcitabine. We searched PubMed/MEDLINE and EMBASE (1997-2015), and the websites of health technology assessment agencies. Two authors independently reviewed economic studies for eligibility in this review; evaluated peer-reviewed, journal-published studies in terms of the Drummond Checklist; and critiqued the technical and scientific merit of all studies. Sixteen pharmacoeconomic evaluations were included: ten published in nine peer-reviewed journals and six on three websites. Six were on single-agent therapies and ten on combination therapies. Analyses conducted included cost-effectiveness (three studies), cost-utility (one study), or combined cost-effectiveness and cost-utility (12 studies). Studies diverged in results, mainly because of different assumptions, methods, inputs, and country-specific guidelines. The two most recent regimens, nanoparticle albumin-bound paclitaxel plus gemcitabine (NAB-P + GEM) and the combination of fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX), were evaluated in an indirect comparison, yielding a statistically similar benefit in overall survival but superior progression-free survival for FOLFIRINOX. NAB-P + GEM showed greater economic benefit over FOLFIRINOX. In conclusion, the divergence in results observed across studies is attributable to economic drivers that are specific to countries and their healthcare (financing) systems. No recommendations regarding the relative economic benefit of treatment regimens, general or country-specific, are made as the purpose of pharmacoeconomic analysis is to inform policy decision-making and clinical practice, not set policy or define clinical practice.