Objective Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment to aortic valve replacement (AVR) for selected patients with severe aortic stenosis. The present systematic review was conducted to analyze the cost-effectiveness of this novel technique within reimbursed healthcare systems. Methods Two reviewers used 7 electronic databases from January 2000 to November 2012 to identify relevant cost-effectiveness studies of TAVI versus AVR or medical therapy. The primary endpoints were the incremental cost-effectiveness ratio (ICER) and the probability of cost-effectiveness. The eligible studies for the present systematic review included those in which the cost-effectiveness data were measured or projected for TAVI and either medical therapy or AVR. All forms of TAVI were included, and all retrieved publications were limited to the English language. Results Eight studies were included for quantitative assessment. The ICER for TAVI compared with medical therapy for surgically inoperable patients ranged from US$26,302 to US$61,889 per quality-adjusted life year gained. The probability of TAVI being cost-effective compared with medical therapy ranged from 0.03 to 1.00. The ICER values for TAVI compared with AVR for high-risk surgical candidates ranged from US$32,000 to US$975,697 per quality-adjusted life year gained. The probability of TAVI being cost-effective in this cohort ranged from 0.116 to 0.709. Conclusions Depending on the ICER threshold selected, TAVI is potentially justified on both medical and economic grounds compared with medical therapy for patients deemed to be surgically inoperable. However, in the high-risk surgical patient cohort, the evidence is currently insufficient to economically justify the use of TAVI in preference to AVR.