To increase understanding of the epidemiology, risks, consequences and resource utilization of Clostridium difficile infection (CDI) in Japan, a systematic literature review was undertaken of relevant publications from January 2006 to November 2017. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and methods, 55 articles met the criteria for full review. The majority (58%) of studies were from a single site, with the most recent data from 2015. The incidence, reported prevalence and recurrence rate of CDI in Japan were 0.8-4.71/ 10,000 patient-days, 0.3-5.5/1000 patients and 3.3-27.3%, respectively, and varied according to setting, population, CDI definition and detection method. Most C. difficile isolates associated with CDI in Japan were toxin A? B?, with a low level of C. difficile binary toxin-positive (CDT?) strains (0-6.8% reported across studies). The most common C. difficile PCR ribotypes associated with infection in Japan were smz/018, 002, 052 and 369. Data regarding the impact of CDI on length of hospital stay were limited. Reported all-cause mortality in patients with CDI ranged from 3.4 to 15.1% between 2007 and 2013. Two studies assessed risk factors for CDI recurrence, identifying malignant disease, intensive care unit hospitalization and use of proton pump inhibitors as factors increasing the risk of initial and/or recurrent CDI. No study analyzed initial CDI treatment in relation to recurrence. More comprehensive surveillance and coordinated studies are needed to map trends, understand risk factors, and recognize the extent and impact of CDI in Japanese patients.