OBJECTIVES: Men with mCRPC are at risk of experiencing SREs, defined as pathologic bone fracture (”fracture”), spinal cord compression (”compression”), and the need for radiotherapy or surgery to bone (”radiotherapy/surgery”). We examined the patient and clinical relevance of SREs for HRQoL in men with mCRPC.  METHODS: We analysed data from patients experiencing any type of SRE (n=587; irrespective of treatment) in PREVAIL - a phase 3 trial of enzalutamide (n=872) vs. placebo (n=845) in asymptomatic/mildly symptomatic chemo-naïve mCRPC patients. For patients with multiple SREs, only the first event was included. HRQoL was assessed using the FACT-P and EQ-5D tools. Impact of first SRE on HRQoL was evaluated as follows: 1) estimate each patient’s longitudinal HRQoL trajectory before the first SRE using repeated measures analysis; 2) calculate how SREs affect HRQoL changes. RESULTS: We found statistically significant declines in utility scores after all three types of SREs with an adjusted mean change of -0.06 (95% CI [-0.10, -0.02]) for “radiotherapy/surgery” (N=107), -0.20 (95% CI [-0.36, -0.04]) for “fractures” (N=31) and -0.24 (95% CI [-0.39, -0.08]) for “compression” (N=23). “Fractures” and “compression” affected a number of FACT-P domains and total score to a clinically meaningful and statistically significant extent. Compression had the broadest impact, affecting 7 out of 9 FACT-P domains and induced a mean decrease in the FACT-P total score of -16.96 (95% CI [-26.47, -7.44]). Radiotherapy/surgery was associated with a statistically significant decline in physical (-1.28, 95% CI [-2.06, -0.50]) and functional well being (-1.51, 95% CI [-2.37, -0.64]), and improvement in social well being (1.26, 95% CI [0.60, 1.91]). Full results will be presented. CONCLUSIONS: The presence of SREs was significantly associated with poorer HRQoL in this patient population. Any therapy reducing or delaying the occurrence of SREs may slow down the observed HRQoL decline in mCRPC patients.