Background: Trimodality therapy (TT) with chemo/radiation (C/RT), chemotherapy and total mesorectal excision (TME) surgery remains the standard for patients with stage 2/3 rectal cancer. Use of pre-operative (pre-op) C/RT is an important Commission on Cancer (CoC) quality benchmark but has not previously been shown to improve overall survival when compared to post-op C/RT. The objective of this study was to document the impact on survival of peri-op C/RT in stage 2/3 rectal cancer in a broad population. Methods: The National Cancer Database was used to identify all patients diagnosed with stage 2/3 rectal cancer from 2006-16. Included patients received true TT and were classified into groups A, Total Neoadjuvant Therapy (TNT) with pre-op C/RT + pre-op multi-agent (MA) chemotherapy (CT); group B, pre-op C/RT+ post-op single-agent CT; group C, pre-op C/RT + post-op MA CT; and group D, post-op C/RT and MA CT. Cox multivariate survival analysis were performed including demographics, peri-op C/RT, surgery type, stage, lymph node count, year of diagnosis and facility type: academic (Acad), Comprehensive (Comp)/Community (Comm), Integrated (Integ) and unknown (Unkn). Results: Of 110,372 stage 2/3 patients, 32,467 received TT (mean age 58, 61% male) and were included. Of these, 8883 (27%, group A) received TNT, 5967 (18%) were in group B, 12,928 (40%) in group C, while 4,689 (14%) were in group D. A reduction in use of post-operative C/RT (group D) was observed between 2006 (28%) and 2016 (8%), p < .001, accompanied by a reciprocal increase in patients receiving pre-op C/RT and post-op MA CT (Group C) between 2006 and 2016 (24 to 45%, respectively, p<0.001). Increasing use of pre-op C/RT led to a migration to lower pathologic stages 0/1/2/3 from 0.60/10/31/57% in 2006, to 2.8/22/29/45% in 2016, respectively (p < .001), while clinical stage 2/3 distribution remained unchanged. Receipt of pre-operative C/RT (Groups A/B/C) was associated with improved survival compared to post-op C/RT (group D) (table). Conclusions: Between 2006-2016 the proportion of patients with stage 2/3 rectal cancer treated with post-op C/RT declined dramatically and in 2016 accounted for 8% of all patients treated with TT. Multivariate analysis documented superior overall survival among patients treated with pre-operative C/RT, justifying the introduction of the CoC quality benchmark.