Abstract Introduction Cardiovascular disease (CVD) and cancer are the top mortality causes globally, yet little is known about how the diagnosis of cancer affects treatment options in patients with hemodynamically compromising aortic stenosis (AS). Patients with cancer often are excluded from aortic valve replacement (AVR) trials including trials with transcatheter AVR (TAVR) and surgical AVR (SAVR). This study looks at how cancer may influence treatment options and assesses the outcome of patients with cancer who undergo SAVR or TAVR intervention. Additionally, we sought to quantitate and compare both clinical and cost outcomes for patients with and without cancer. Methods This population-based case-control study uses the most recent year available National Inpatient Sample (NIS (2016) from the United States Department of Health and Human Services’ Agency for Healthcare Research and Quality (AHRQ). Machine learning augmented propensity score adjusted multivariable regression was conducted based on the likelihood of undergoing TAVR versus medical management (MM) and TAVR versus SAVR with model optimization supported by backward propagation neural network machine learning. Results Of the 30,195,722 total hospital admissions, 39,254 (0.13%) TAVRs were performed, with significantly fewer performed in patients with versus without cancer even in those of comparable age and mortality risk (23.82% versus 76.18%, p