Background: Sip-T is a cellular immunotherapy approved for treatment of asymptomatic/minimally symptomatic mCRPC on the basis of improved OS. Across 4 clinical trials, CVEs occurred in 3.5% of sip-T vs 2.6% of control pts. The PROCEED registry (NCT01306890) assessed the risk of CVEs after sip-T treatment in mCRPC pts. Methods: Pts with mCRPC scheduled to receive sip-T or who had received sip-T ≤6 months prior were eligible. Treatment consisted of 3 sip-T infusions ~2 weeks apart. Primary objective was to define CVE risk after sip-T treatment. Secondary objective was to quantify OS. Follow-up was every 3 months after sip-T for a minimum of three years, death, or until otherwise off study. Results: Between 2011–2017, 1976 pts enrolled; median age 72 years; 87% Caucasians, 12% African American; 84% had bone, 32% lymph node, 4.6% visceral metastases. 1813 (95%) pts had all 3 and 1902 had ≥1 sip-T infusions. 1763 (93%) pts had CVE risk factors, including smoking (54%), alcohol use (57%), hypertension (65%), cardiovascular disease (61%). Median follow-up was 46.5 months. Of 1902 pts, 54 (2.8%) had a CVE (excluding transient ischemic attacks) after sip-T therapy or CVE rate (95% confidence interval [CI]) of 1.2 (0.9–1.6)/100 person-years compared with 1.52 (1.37–1.70)/100 person-years in 11,972 mCRPC pts from the SEER-Medicare database (1999–2013). Grade 3–4 catheter-related infection or sepsis was 0.4 and 0.2%, respectively, with no grade 5 catheter-related adverse events. Median OS was 30.7 (95% CI 28.6, 32.2) months. Of 1255 deaths, 77% were due to mCRPC progression with a median time to death from disease progression of 42.7 months (95% CI 39.4, 46.2). CD54+ counts, CD54 upregulation, and total nucleated cell counts in the sip-T product significantly correlated with OS, p < 0.001, hazard ratio (HR) 0.82, (95% CI 0.76, 0.93), p < 0.001, HR 0.51 (95% CI 0.44, 0.60), and p < 0.001, HR 0.57 (95% CI 0.50, 0.64), respectively. Conclusions: There was no excess rate of CVEs in men with mCRPC treated with sip-T compared with those who were not. In vitro immune activation measured in the sip-T product significantly correlated with OS. Clinical trial information: NCT01306890