Abstract Background Cancer patients are at an increased risk for C. difficile infection (CDI) which is often identified along with other enteropathogens. The impact of co-infections on outcomes has not been established in this population. We compared the risk factors and clinical characteristics of patients with CDI monoinfection (CDIM) and patients coinfected with bacterial (CDIB) or viral (CDIV) enteropathogens. Methods Adult patients presenting with primary or recurrent CDI (n = 88) identified on a two-step GI multiplex assay (Biofire) followed by toxin A/B EIA, were classified into CDIM (n = 66), CDIB (n = 12), and CDIV (n = 10) groups. Demographic and clinical data were collected and risk factors and outcomes compared by Fisher’s exact test, ANOVA, and the Kruskal–Wallis test. CDI severity was determined using Zar’s criteria, presence of bacteremia, and ICU stay. Results During the study period, 2,017 diarrheal samples were submitted to the microbiology laboratory. An enteric pathogen was identified in 311 (15%) patients. CDI was identified in 88 cases of which 22 (25%) had a second pathogen. CDIM was found in 66 (21%), CDIB in 12 (4%), and CDIV in 10 (3%) subjects. The most common co-pathogens identified were diarrheagenic E. coli in the CDIB group (9/12, 75%) and norovirus in the CDIV group (8/10, 80%). Groups were similar in terms of demographics, number of recurrences, health care acquisition, co-morbidities, disease severity, serum creatinine at presentation, presence of toxin by EIA, and mortality. Patients with CDIM were more likely to have a recent hospitalization than the CDIB group (44/66 67% vs.. 3/12 25%, P = 0.01). Clinical symptoms at presentation were similar for the three groups except for nausea which was more common in the CDIV group when compared with CDIM (8/10, 80% vs. 25/66, 38%; P = 0.02). The use of proton pump inhibitors was similar in the three groups. There was however, a higher proportion of patients taking GABA-like drugs within 90 days among the CDIB patients (10/12, 83%) than the group with CDIM (26/66, 40%) P = 0.01. Conclusion In CDI cancer patients, co-infection with other enteropathogens is common. Patients with CDIB were less likely to have a recent admission to a health care facility. The use of GABA-like drugs was associated with a higher risk of bacterial co-infection. Disclosures All authors: No reported disclosures.