The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 μg, and 4, 3, and 2 weeks reaching 100 μg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.