OBJECTIVES: To perform a health technology assessment (HTA) commissioned by the German Federal Ministry of Health on coronary fractional flow reserve (FFR) to guide the decision on coronary stenting in patients with suspected mild coronary artery disease (CAD). METHODS: We performed a systematic literature search to identify clinical and economic studies on FFR-guided strategies. A meta-analysis on the diagnostic value of FFR and a review on economic evaluations were done. We developed a decision-analytic Coronary Artery Disease Outcome Model (CADOM) for the German health care context. Patients with angiographically suspected CAD without confirmed diagnosis were modeled in subgroups for age and gender (basecase: 60-year old man). Model parameters were derived from German databases and the published literature. We adopted the societal perspective, used a life-time horizon, and discounted costs and effects by 5% per year. RESULTS: We identified 10 diagnostic accuracy studies, 1 multicenter randomized clinical trial (RCT) for efficacy, and 1 decision-analytic cost-effectiveness study (US context). Pooled sensitivity and specificity of FFR was 81.7% (95%CI: 77.0-85.7%) and 78.7% (95%CI: 74.3-82.7%), respectively. Few studies used a sufficient goldstandard. The RCT investigated the efficacy of a FFR-based treatment strategy and showed advantages for patients in terms of major adverse cardiac events and freedom from angina. The cost-effectiveness study showed the FFR-based strategy being cost-saving in the US health care system. Results from German CADOM indicated a gain in (quality-adjusted) life-expectancy for the FFR-guided strategy compared to universal coronary intervention in all patients. The base-case discounted incremental cost-effectiveness ratio was Euro 16,000 per QALY gained. Uni- and multivariate sensitivity analyses showed robust results. CONCLUSION: This HTA suggests that FFR-guided treatment results in clinical benefits for patients with suspected CAD and should be cost-effective in the German context. FFR should be implemented in routine clinical decision making in patients with suspected CAD.