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Purpose Adherence to growth hormone (GH) treatment impacts clinical outcomes. The aim of this study is to assess the impact of adherence to rhGH treatment (2 years) on auxological outcomes. Methods Multicentric, retrospective observational study in rhGH-naive GHD/SGA children treated with Saizen (R) during >= 2 years. Growth response was assessed by evaluating the change in height standard deviation score (Delta H SDS) and the index of responsiveness (IoR). Adherence was monitored using EasyPod (TM) Connect device. Results A total of 110 patients (3 Spanish centers) were evaluable (GHD n = 76, SGA n = 34). Adherence was 95.6 and 93.9% (year 1, 2). SGA and GHD children showed an increase of 0.6 cm/year and 1.1 cm/year for each 10% adherence modification. Lower adherence was observed in patients with lower pretreatment height velocity (HV) and in patients whose parents had a lower level of education. A positive correlation between index of responsiveness (IoR) during the first and second years with HV SDS during the second year and between IoR2 and adherence (year 1, 2) was observed. The frequency of patients with HV > 1 SD was higher (p = 0.025) among patients with adherence >90%. The best model to predict the height gain(cm) reaching an adjusted R squared of 0.489 involved percentage of adherence, Tanner stage, pretreatment HV, dose of rhGH, and whether the treatment was initiated before or after puberty. Conclusions Adherence during the first 2 years of response was very high >90% and showed a negative association with age, pretreatment HV and treatment duration and a positive correlation with the level of parent education.