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Background Specific immunotherapy for hymenoptera venom allergy (venom immunotherapy [VIT]) is safe and effective. The duration of treatment is still open for discussion because there is no reliable routine test to determine the real risk of serious anaphylactic reactions. This prospective study, which spans more than 25 years, was conducted to ensure unlimited protection through continuous VIT. To reduce workload and cost, the maintenance interval was increased to 6 months without increasing the rate of adverse events. Only patients with continuous follow-up by our service were included in this study. Patients and methods VIT was conducted in 176 patients (125 allergic to wasp venom, 20 to bee venom, 31 to both) over a mean of 7.14 years (1.16-25.49). Total and specific IgE were determined on a regular basis. Results A total of 162 re-stings were reported. Of these, 154 produced a strictly local reaction, seven produced non-serious reactions and one produced a systemic reaction similar to that produced by the initial sting before VIT. Total and specific IgE diminished during VIT. Substantial adverse effects were rare and never life-threatening. The effects occurred during observation in the ward and were controlled according to the treatment protocol recommended by a German expert consensus meeting on the treatment of anaphylactoid reactions. VIT was terminated in only one patient due to recurrent adverse effects. Conclusion Continuous VIT at 6-monthly maintenance intervals conferred permanent protection in patients allergic to bee and wasp venoms and was found to be a safe and effective alternative to current standard protocols.