Rationale, aims and objectives. The prognostic value of baseline clinical parameters in predicting the survival prolonging effect of 223Ra-therapy in metastatic Castration Resistant Prostate Cancer patients is still an open issue. The aim of this study was investigating the impact of baseline Quality of Life on Overall Survival (OS) in mCRPC patients treated with 223Ra. The present study also evaluated the trend of patient-reported QoL during both 223Ra-treatment and post-therapy follow-up period. Method 173 consecutive mCRPC patients treated with 223Ra were included in this prospective study. QoL was assessed through EORTC QLQ-C30 and QLQ-BM22 Questionnaires and 2264 questionnaires were evaluated. Other baseline variables relevant to the OS analysis have been considered. Data were summarized using descriptive statistics, univariate and multivariate analysis with Cox model. A principal component analysis (PCA) on the questionnaires’ results compiled at baseline was performed to reduce the data to a one-dimensional score. Joint models for survival and longitudinal data were finally used in order to evaluate the relationship between the time-depended QoL scores and OS. Results On multivariate analysis, baseline patients’ Hb, tALP, and two EORTC QLQ-C30 items, physical functioning (HR=0.970,CI=0.960-0.980,p0.001) and dyspnea (HR=0.992,CI=0.986-0.999,p=0.023), were significantly associated with OS. In the resulting model of the multivariate analysis performed after PCA, baseline patients’ Hb, tALP and QoL-score were independent significant predictors of OS (QoL-score:HR=0.995-95%CI=0.992 – 0.998,p=0.001). The OS analysis stratified by score of baseline QoL, showed a median OS of 8 (95%CI=6-11) and 16 (95%CI=12-24) months for scores respectively below and above the cut-off value (log-rank-p<0.001). The joint model showed a significant deterioration of QoL-score during both 223Ra-therapy and follow-up period (p<0.001).Conclusion Baseline QoL is a significant predictor of OS, meaning that patients with better pretreatment QoL are more likely to obtain a marked survival prolonging effect from 223Ra.