OBJECTIVES: To systematically review the current clinical and cost-effectiveness literature of third-generation, implantable left ventricular assist devices (LVADs) for people with end-stage heart failure (ESHF). METHODS: Three implantable, third-generation LVADs were identified as available in the EU. A systematic literature review was conducted of published and unpublished cost-effectiveness and clinical data (comparative studies) in the ESHF population, since their inception till April 2012, using a number of medical databases. RESULTS: One relevant economic evaluation and four comparative clinical studies (1 vs. virtual control arm & 3 vs. older-generation LVADs) met the inclusion criteria. Therapy success defined as survival LVAD or explant to receive a heart transplant or for recovery, occurred in approx. 92.0% of patients with third-generation LVADs and 90.1% of control patients (second-generation LVAD) in a 6-months period. The 1-year survival of patients who were implanted with third-generation LVADs ranged from 82% to 91%. The most frequently reported adverse events were arrhythmias, bleeding, infection, respiratory and renal failure, right heart failure, and stroke. One included study evaluates the cost-effectiveness of the implantable, third-generation LVADs as destination therapy for patients with ESHF as compared to patients on medical management in the UK. Results showed that at 5ys LVADs had an additional cost of about £20,500 per patient and QALY gain of 1.05, giving an incremental cost per QALY of £19 500, which is below the commonly adopted threshold of £25,000 per QALY. However, this finding seems unreliable due to controversial assumptions. CONCLUSIONS: Despite the poor methodological quality of included studies, third-generation of implantable LVADs seems beneficial due to improving survival, therapy success and functional status. Adverse events serious concern. No prospective controlled data are available as bridge to recovery, nor destination therapy. There is an urgent need for additional, reliable cost-effectiveness studies evaluating third-generation pumps versus previous generations of LVADs.