Summary The ongoing mission of the NIAAA-funded Consortium to improve OutcoMes in hiv/Aids, Alcohol, Aging, and multi-Substance use (COMpAAAS) is to build and disseminate the evidence needed to optimize care for HIV+ individuals experiencing medical harm from alcohol and related substance use through coordinated, integrated, and externally validated observational, OR modeling, and intervention studies. Over the past 5 years, we have coordinated two meetings of the entire CHAART consortia (a third scheduled February 2016) and successfully conducted coordinated observational research, operations research (OR) modeling and intervention studies focused on the role of alcohol and multisubstance use in determining modifiable outcomes among HIV+ and uninfected individuals. Our highly effective Coordinating Center at the West Haven VA Medical Center has facilitated the expansion of our productive network of investigators and collaborators. Over the past 15 years, our group has produced >250 publications and these were cited >1,700 times in 2014. Our work has directly influenced VA and national guideline development and has provided essential insights into HIV, aging and alcohol and multisubstance use. We are proud of the education, training, and career development support we offer. COMpAAAS goals for the next 5 years build on our prior work and include: developing unbiased estimates of the effect of polypharmacy, potentially inappropriate medications (PIMs), alcohol use, and treatment for Alcohol Use Disorder (AUD) and hepatitis C (HCV) to inform simplification and prioritization of pharmaceutical treatment (COMpAAAS U01: Observational Study); expanding our alcohol intervention studies using contingency management and addressing the interaction between alcohol use and medical conditions (COMpAAAS U01: Intervention Study); and use Operations Research modeling to understand the implications of various approaches to screening for alcohol use prior to HCV treatment (COMpAAAS U01: OR Modeling Study). Drawing on prior experience, our extensive network of investigators, collaborators, trainees, policy makers, and patients, this U24 proposal (COMpAAAS U24: Coordinating Center) will coordinate, support, and inform the 3 U01 projects and 2 U24 Resource Centers (COMpAAAS U24: RIB and COMpAAAS U24: CHAMP) with resources, information, technologies, ideas, and expertise to greatly enhance their impact.