Introduction: Cystic fibrosis related diabetes (CFRD) is the result of a partial to complete insulin deficiency, leading to hyperglycaemia, loss of muscle mass and catabolic state. Insulin is the only recommended therapy and continuous subcutaneous insulin infusion (CSII) systems are gaining evidence to be the best treatment, leading to a better glycemic control and an improvement in muscle mass. Today, data concerning automated hybrid closed loop (AHCL) systems in CFRD are still lacking. Aim: to evaluate the effects of insulin therapy optimization with AHCL systems on glycemic control in people with CFRD, already on insulin treatment (CSII) or multiple daily injections – MDI) and already trained with a structured educational program for the management of their therapy (training to MDI/CSII and carbohydrates counting). Methods: 14 patients (7 F/7 M) agreed to participate in the study and switched to AHCL (7 from a CSII system/7 from MDI). All individuals wore a continuous glucose monitoring (CGM) at enrollment. At baseline and after 6 months patients had a blood sample for biochemistry and data were downloaded from their CGM. A mid-term evaluation of data from CGM was performed 4 weeks after baseline. Results: We demonstrated a substantial improvement in glucose control at end of trial (HbA1c 7.1±0.9 to 6.2±0.6%, p<0.01; glucose 7.9±3.0 to 6.3±2.8 mmol/L, ns; average glucose – AG 8.7±1.7 to 8.4±1.2 mmol/L, ns; Glucose management indicator - GMI 7.5±0.9 to 6.9±0.5%, p<0.05; time in range – TIR 58.2±22.3 to 77.0±15.0%, p<0.01; coefficient of variation – CV: 35.5±8.0 to 30.3±4.8, ns). The improvement in the CGM parameters was already relevant at the mid-term analysis (AG 8.7±1.7 to 7.9±1.1 mmol/L, ns; GMI 7.5±0.9 to 6.6±0.5%, p<0.01; TIR 58.2±22.3 to 77.6±11.9%, p<0.01; CV: 35.5±8.0 to 30.4±5.2, ns). AHCL systems lead to a significative improvement in glycemic control in CFRD and, as for type 1 DM, should be proposed as gold standard therapy, considering the pivotal role of an enhanced glycemic management in body composition and, eventually, long term outcomes in this population.