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Background: Geographic and temporal trends in the distribution of PCR ribotypes for Clostridioides difficile associated diarrheal isolates obtained in the United States (US) are changing. As part of a US national surveillance program of C. difficile susceptibility to fidaxomicin, we quantified the distribution of PCR ribotypes of stool isolates collected from 2011 to 2016., Methods: C. difficile isolates or C. difficile toxin + stools from patients with C. difficile infection (CDI) were submitted for testing to Tufts Medical Center from 6 geographically distinct medical centers. Following isolation and confirmation as C. difficile, approximately 35% of the isolates were randomly sampled, stratified by center, for PCR ribotyping by capillary gel electrophoresis. Toxin gene profiling was performed on all isolates., Results: 939 isolates from a total of 2814 (33.4%) isolated over the 6 years were analyzed. Seventy unique ribotypes were observed, including 19 ribotypes observed 10 or more times. Sixteen ribotypes were not previously observed in our data base. Ribotype 027 declined by more than 60% over the 6 years of the survey from 35.3% to 13.1% (p < 0.001). Ribotype 106 was the most common in 2016, followed by 027 and 014-020. There were strong correlations between 027 and binary toxin with the 18 base pair deletion of tcdC and ribotype 078-126 had 100% concordance with the previously described tcdC 39 base pair deletion., Conclusions: The frequency of ribotypes in the US has changed with a marked decline in 027. Each of the geographical areas had variations which differed from each other, but collectively, these results suggest that the changing epidemiology of C. difficile in the US is consistent with what is being seen in Europe. Continued surveillance and monitoring of changes in ribotype distributions of C. difficile are warranted., Competing Interests: Declaration of competing interest Dr. Dale N Gerding is a member of the Advisory Board for Merck. Dr. Ellie Goldstein has been on advisory boards for Merck, Summit Therapeutics, LLC. He has been on a speaker bureau for Merck. Dr. Stephen G. Jenkins has no conflicts of interest as they relate to this project. Dr. Stuart Johnson has no conflicts of interest related to this project. Ms. Laura McDermott has no conflicts of interest as they relate to this project. Dr. Robin Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited and Shionogi. Dr. Patel is a consultant to Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Selux Diagnostics and Qvella; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Dr. Patel receives travel reimbursement from ASM and IDSA, an editor's stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. Dr. David R. Snydman has current research funds from Merck, Pfizer and Summit Therapeutics, LLC. Dr. Snydman has been an advisor to Merck, and Summit Therapeutics, LLC. Dr. Cheleste M. Thorpe has received research funds from Merck (formerly Cubist/Optimer), Actelion, and Summit Therapeutics, LLC. She has also been on a Summit Advisory Board and received a travel grant from Summit Therapeutics, LLC. Dr. Seth T. Walk has no conflicts of interest to report., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)