Introduction: Pts with CKD on HD (HD) have an increased incidence of C. difficile infection (CDI) and higher recurrence rate compared with those not on HD (NoHD). With the evolving epidemiology of CDI, it is unclear whether these trends persist. We hypothesize that recurrence rates in HD will remain higher than NoHD regardless of therapy. Methods: We identified consecutive pts with a +C. difficile toxin assay and symptomatic diarrhea at Yale-New Haven Hospital between 4/10 and 12/15. For each pt we recorded demographics, co-morbidities, lab data at diagnosis, treatments and outcomes (e.g. 30-day mortality, 30-day colectomy, sepsis, 30- and 90-day recurrence). Pts were grouped into HD and NoHD and were compared (SPSS 23.0). Results: Of 1206 pts, 96 had CKD on HD and 1110 were NoHD.There were no significant differences in age, but HD had less Caucasians (P<0.001) and more African Americans (P< 0.001). The HD cohort had a higher Charlson Co-morbidity score (5.9 ± 2.7, 3.9 ± 3.0, P<0.001) and higher frequency of DM (P<0.001) compared with NoHD.There were no differences in vital signs, presenting symptoms or workup of disease. Treatment patterns with metronidazole (MZO), vancomycin (VCO) and combination (COM) were similar. HD had higher all-cause readmission at 30-day's (45.0%, 28.6%, P<0.001) and 90-day's (53.9%, 37.9%, P<0.01) and higher recurrence at 30-day's (11.3%, 7.3%, P< 0.001) and 90-day's (13.8%, 8.9%, P<0.001) compared with NoHD. 30-day mortality showed a trend for higher levels in HD (14.3%, 9.9%, P=0.4) but 6-month mortality was higher in NoHD (24.2%, 27.4%, P<0.001).In those who received only MZO, 30-day recurrence was higher in HD than NoHD (15.6%, 4.6%, P<0.001); a similar but not statistically significant trend was seen at 90-days (15.6%, 5.5%, P=0.1).In those treated with only VCO, 90-day recurrence was higher in HD compared with NoHD (15.4%, 8.4%, P<0.01) whereas 6-month mortality was lower in HD (16.7%, 27.5%, P<0.01).No differences were seen in recurrence or mortality in those treated with COM. Conclusion: Recurrence in HD remains elevated compared with NoHD. Pts treated with MZO are at risk of increased short-term recurrence while VCO are at risk for longer-term recurrence. Aggressive initial treatment of pts on HD and risk factor reduction for recurrence might optimize outcomes for these pts. Further research is needed to delineate optimal management.