Background: Emergency department visits and hospitalizations are common in patients with cancer, with nearly three quarters of patients with advanced disease hospitalized at least once in the year after their diagnosis. Efforts to prospectively identify patients at highest risk for this acute care utilization (ACU) are needed. While many risk scoring systems have been developed for this purpose, few have been effectively integrated into clinical practice. We piloted a prospective risk assessment tool using a quality improvement framework. Methods: We utilized our previously published REDUCE score (Reducing ED Utilization in the Cancer Experience) to pilot clinical interventions to reduce ACU using PDSA cycles. Cycle 1 included a chart review and targeted outreach by a nurse navigator to high risk patients identified by REDUCE. Outreach resulted in communication of patient needs to the care team, which may or may not have resulted in additional interventions. Cycle 2 involved initial identification by REDUCE followed by further assessment with a distress screening. Those who were high risk and had high distress (score ≥4) were discussed by an interdisciplinary team (including supportive medicine physicians, social work, nurses, nurse practitioners) to determine an appropriate intervention. Results: Of the patients in Cycle 1 (N = 138), 26.1% had ACU after outreach by a nurse navigator, while in Cycle 2 (N = 169) 7.1% had ACU after the intervention determined by the interdisciplinary team. The average distress score among all patients in Cycle 2 was 6.0 and the REDUCE score was 2.87, while the subset of patients who experienced ACU had an average distress score of 6.4 and a REDUCE score of 3.22. Conclusions: The REDUCE score may be a valuable tool to assist in identifying patients at risk for ACU. We found that combining the risk score with a biopsychosocial screening tool and multidisciplinary team discussion may prove more valuable than the risk score alone, with Cycle 2 findings suggesting that there is a directional correlation between REDUCE score and distress screening results. More work is needed to understand the relative impact of the REDUCE score and the biopsychosocial screening and team discussion on decreasing ACU.