OBJECTIVES: To assess the relative effects and costs of Oralair® versus Grazax®, ALK Depot SQ® (alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinitis; based on a systematic literature review, meta-analysis and cost-effectiveness analysis. METHODS: The costs and effects of three year treatment were assessed for a period of 9 years using a Markov model. Efficacy was estimated using an indirect comparison of available clinical trials. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug acquisition costs, resource use and other medical costs were derived from published sources. The analysis was conducted from the German payer’s perspective, including Statutory Health Insurance (SHI) payments and co-payments by insurants. Effects were reported as quality adjusted life years (QALYs) and symptom-free days (SFDs). The uncertainty around the incremental model outcomes was tested by means of extensive deterministic univariate and probabilistic sensitivity analyses; various scenario analyses were also conducted. RESULTS: In the base case analysis the model predicted a cost-utility ratio of Oralair® versus symptomatic treatment of €14,728 per QALY: incremental costs were €1,356 (95%CI: €1,230;€1,484) and incremental QALYs 0.092 (95%CI: 0.052;0.140). Oralair® was the dominant strategy compared to Grazax® and ALK Depot SQ®, with estimated incremental costs of -€1,142 (95%CI: -€1,255;-€1,038) and -€ 54 (95%CI: -€188;€85) and incremental QALYs of 0.015 (95%CI: -0.025;0.056) and 0.027 (95%CI: -0.022;0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of Oralair® being the most cost-effective treatment was predicted to be 79%. The univariate sensitivity analyses show that the results were especially sensitive to changes in transition probabilities of immunotherapy discontinuation and efficacy estimates. Calculations on SFDs showed a comparable cost-effectiveness trend. CONCLUSIONS: The analysis suggests Oralair® to be cost-effective compared to Grazax®, ALK Depot SQ® and symptomatic treatment. The robustness of these statements has been confirmed in extensive sensitivity analyses.