Background: Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions. Objective: To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites. Methods: An open-label, non-controlled, non-randomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-minute interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months. Results: Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects. Conclusions: SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile. Keywords: allergic asthma, allergic rhinitis, Blomia tropicalis, Dermatophagoides pteronyssinus, House dust mites, Lepidoglyphus destructor, maximum extract concentrations. safety,