BACKGROUND: Fenestrated endovascular aneurysm repair (fEVAR) is a new endovascular approach for complex abdominal aortic aneurysms (cAAAs). OBJECTIVES:  We assess the clinical and cost-effectiveness of fEVAR compared to open surgical repair (OSR) in cAAAs. Additionally, we characterize key sources of uncertainty, quantify their impact on cost-effectiveness, and discuss how they influence the adoption decision and need for further research. METHODS:  A systematic review, meta-analysis, and a four state Markov model were used to estimate the cost-effectiveness of fEVAR versus OSR in male patients with cAAAs. We used a recently developed coverage with evidence development framework to characterize the relevant sources of uncertainty and to determine the value of conducting further research. This was also used to determine the decision option (accept, reject, accept with research (AWR), or only in research (OIR)) which maximises net population benefit (NPB). RESULTS:  Seven observational comparative studies were identified, with a pooled odds ratio of 0.34 (95% CI: 0.19 to 0.61, random effects) for mortality in favour of fEVAR compared with OSR. The incremental cost per quality adjusted life year (QALY) was estimated to be over £55,712/QALY, with a very low probability of 0.076 that fEVAR would be considered cost-effective at a threshold of £30,000 per QALY. At this threshold, there is no value of information from a new RCT; however at higher thresholds of £38,000 – £55,000/QALY the model predicts OIR as an appropriate decision option to reduce uncertainty. CONCLUSIONS:  Based on current evidence, fEVAR is not a cost-effective option compared to OSR at standard acceptable cost-effectiveness thresholds in the UK. In jurisdictions with a higher cost-effectiveness threshold used in decision-making, an OIR decision might be warranted.