Background: Clinical and laboratory factors, i.e. visceral metastasis, anemia, LDH, PSA, PSA-doubling time, bone scan progression, pain, performance status (PS), are recognized to be prognostic factors for overall survival (OS) in metastatic castration resistant prostate cancer (mCRPC). We sought to determine if the Charlson comorbidity Index (CCI) and hypertension (HTN) provide prognostic information independent of these known factors. Methods: We retrospectively evaluated 221 patients with mCRPC treated with docetaxel plus prednisone (DP) combined with AT-101 (bcl-2 antagonist) or placebo on a randomized phase II trial. Both arms of the trial were combined since no differences in outcomes or toxicities were observed. Wilcoxon rank sum test and Fisher’s exact tests were used to compare data by comorbidity groups (CCI as a continuous variable, CCI = 6 vs. CCI ≥7 and HTN vs. no HTN). Cox regression analysis was done to identify whether CCI or HTN independently predicted OS after adjusting for trial stratification factors (pain, performance status), nomogram, risk-groups and PCWG-2 clinical sub-types. Results: CCI was 6 in 116 patients (52.7%) whereas it was 7 in 70 (31.8%), 8 in 23 (10.5%), 9 in (1.8%) and 10 in 7 patients (3.2%) respectively. HTN was present in 107 (48.6%) patients. Patients with HTN had increased CCI (mean CCI 7.0 vs. 6.43, p < 0.001). Patients with CCI of ≥7 were older and exhibited worse ECOG-PS and anemia than patients with CCI of 6 (p<0.05). CCI was not found to be independently predictive of OS on univariable and multivariable analyses. HTN alone or in combination with CCI was borderline significantly associated with OS (p~0.08) on both univariable and multivariable analyses. Conclusions: CCI did not predict OS independent of known prognostic factors in mCRPC. Age, performance status and anemia may adequately capture comorbidities in the context of mCRPC, given their association with higher CCI. Further analysis of HTN in a larger dataset may be warranted given its borderline independent association with OS.