SUMMARY. Aim. The aim of this study was to assess possible predictors of poor adherence in patients with a diagnosis of schizophrenia-spectrum disorders (SD) or bipolar disorder (BD) and to evaluate the roles of attachment style and caregivers as predictive factors of adherence. Methods. The sample was composed of 178 voluntarily hospitalized inpatients: 89 diagnosed with BD (I, II), 89 with SD and other schizophrenia-spectrum disorders. All patients enrolled in the study were assessed for adherence, psychopathology, attachment style, presence of caregiver, subjective well-being during pharmacological treatment with neuroleptics, side effects following therapy, subjective attitude towards drugs, global functioning and quality of life. Results. In patients with SD, non-adherence was associated with the absence of a caregiver, fewer years of treatment, poor insight and attitude towards drugs and fearful dimensions of attachment. In patients with BD, poor insight, anxious and social avoidant temperament traits, together with a high sense of self efficacy, were related to non-adherence. Diagnosis, type of medication and side effects were not predictive factors of adherence in either group. Interestingly, some temperament traits and dimensions of attachment predict non-adherence, indicating differences between patients with SD and BD. Conclusion. Considering these predictors of non-adherence and assessing adherence at the time of admission for relapse could be useful to plan an early and tailored “treatment adherence”, along with other therapeutic strategies, for patients using these predictive factors. The role of caregiver proved particularly important in relation to the therapeutic alliance. Attachment style may play a key role in predicting adherence through the therapeutic alliance with both patients and caregivers.