Background: Aspirin has an established role in preventing CRC. Recent data suggests aspirin use may also benefit a subset of pts diagnosed with CRC. In one series, the authors identified PIK3CA mutations as a potential predictive biomarker for aspirin use, reporting that PIK3CA mutant CRC pts receiving aspirin had superior cancer specific survival (CSS) compared to those not receiving aspirin (HR 0.18, p<0.001), whereas in pts with wildtype PIK3CA, aspirin had no survival impact. Our study aims to confirm the survival benefit associated with aspirin use in pts with PIK3CA mutant CRC. Methods: A cohort of CRC pts with PIK3CA mutations (Sanger sequencing) was identified. Prospectively collected clinicopathological, treatment and outcome data was available. Aspirin use was confirmed by chart review. CSS and overall survival (OS) analyses were conducted using Cox proportional hazards in univariate and multivariate settings. Recurrence free survival (RFS) analyses were limited to early stage CRC pts (Stage A-C). Statistical differences in 5-year CSS (5YS) rates were calculated using Fisher’s exact test. Results: From a cohort of 1,019 CRC pts with known PIK3CA mutation status, 121 (12%) harbored PIK3CA mutations. Of these, 112 (92%) had aspirin usage data available: 27 (24%) pts used aspirin, 85 (76%) did not. In the aspirin group, there were 22 (81%) early stage and 5 (19%) metastatic CRC pts; in the no-aspirin group, there were 59 (69%) early stage and 26 (31%) metastatic CRC pts. In univariate analyses, aspirin use was not associated with superior CSS (HR 0.57, p=0.21), OS (HR 0.83, p=0.57), or RFS (HR 0.72, p=0.57). In multivariate analyses, aspirin use was not associated with improved OS (HR 1.07, p=0.86), CSS (HR 1.04, p=0.94) or RFS (HR 0.54, p=0.34). In 69 (62%) pts with mature follow-up, there was a trend towards superior 5YS for aspirin users (69% v 42%, p=0.09), but this may reflect imbalances in stage at diagnosis. Conclusions: Our study was unable to confirm the recently reported survival benefit associated with aspirin use in pts with PIK3CA mutant CRC. Given the small numbers of pts, a modest survival benefit associated with aspirin use cannot be excluded. Analyses in an expanded cohort of early stage pts are underway.