Background: Anaphylaxis is a severe, life-threatening generalised or systemic hypersensitivity reaction with high mortality. Specialist services (SSs) are believed to reduce anaphylaxis recurrence and improve use of adrenaline injectors (AIs), which can reduce mortality if used correctly and in time. Objectives: To review the evidence on which persons are at high risk of anaphylactic episodes, the effects of history-taking (including signs, symptoms and physical examination) for anaphylaxis, and when (suspected) patients should be referred. To assess the cost-effectiveness of SS compared with standard care (SC) with or without prescription of AIs. Data sources: In order to assess the clinical effectiveness, 10 databases [Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), NHS Economic Evaluation Database (NHS EED), Science Citation Index (SCI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, from inception up to March 2011] were searched without data restriction in order to identify relevant studies [randomised controlled trials (RCTs), controlled clinical trials, observational studies, prognostic studies using a multivariate model] written in English. Review methods: Standard review methods were applied for the assessment of clinical effectiveness. A Markov model, validated by clinical experts, was constructed, which modelled anaphylaxis according to trigger: either food, drug, insect or idiopathic. Anaphylaxis mortality was modelled as a function of time to die and time for emergency response. Probabilistic sensitivity analysis on key parameters was performed. Results: From the systematic review, 11,058 references were identified by the searches for studies assessing the clinical effectiveness. In total, 107 papers were obtained, and five prospective observational studies, including 1725 patients, were included. These studies estimated the risk of recurrence to be between 30% and 42.8%. In children (< 12 years), an overall recurrence of 27% was reported, with food being the most frequent allergen (71%). From the cost-effectiveness analysis (CEA), SC with injectors was dominated by SS with or without injectors. SS with no injectors would be cost-effective if the threshold for a quality-adjusted life-year (QALY) was greater than about £740 and with injectors would be cost-effective if the threshold was > £1800. These results were robust to all sensitivity analyses except at relatively extreme values of a small number of parameters. Limitations: Limitations of the study include the low yield from the systematic review; in particular there were no good-quality studies of either SSs or AI effectiveness. This implied a great reliance on expert opinion in the CEA. However, this was appropriately addressed using sensitivity analysis. Conclusions: Only five observational studies assessing clinical effectiveness were identified. Owing to the lack of good data to inform the effectiveness of anaphylaxis intervention, we recommend considerations of RCTs or at least well-designed observational studies of the components of care in SSs. The results of the CEA showed that SS with AIs was cost-effective at a threshold of £20,000 per QALY. More well-designed prospective studies on the effectiveness of SSs are needed to confirm these findings.