AIM: To date, there has been little systematic assessment of the quality of care associated with systemic anti-cancer therapy (SACT) delivery across national healthcare systems. We evaluated hospital-level toxicity rates during SACT treatment as a means of identifying variation in care quality. METHODS: All colorectal cancer (CRC) patients receiving SACT within 106 English National Health Service (NHS) hospitals between 2016 and 2019 were included. Severe acute toxicity rates were derived from hospital administrative data using a validated coding framework. Variation in hospital-level toxicity rates was assessed separately in the adjuvant and metastatic settings. Toxicity rates were adjusted for age, sex, comorbidity, performance status, tumour site, and TNM staging. RESULTS: Eight thousand one hundred and seventy three patients received SACT in the adjuvant setting, and 7,683 patients in the metastatic setting. Adjusted severe acute toxicity rates varied between hospitals from 11% to 49% for the adjuvant cohort, and from 25% to 67% for the metastatic cohort. Compared to the national mean toxicity rate in the adjuvant cohort, six hospitals were more than two standard deviations (2SD) above, and four hospitals were more than 2SD below. In the metastatic cohort, six hospitals were more than 2SD above, and seven hospitals were more than 2SD below the national mean toxicity rate. Overall, 12 hospitals (12%) had toxicity rates more than 2SD above the national mean, and 11 (10%) had rates more than 2SD below. CONCLUSION: There is substantial variation in hospital-level severe acute toxicity rates in both the adjuvant and metastatic settings, despite risk-adjustment. Ongoing reporting of this performance indicator can be used to focus further investigation of toxicity rates and stimulate quality improvement initiatives to improve care.