Objective To analyze the influencing factors of Clostridium difficile infection (CDI) in elderly hospitalized patients. Methods The clinical data of 114 inpatients with abdominal pain, abdominal distension and diarrhea admitted to our department from November 2013 to September 2021 were collected and retrospectively analyzed. Clostridium difficile toxin was detected with multiplex polymerase chain reaction. According to the results, the patients were divided into a toxin-negative group (n=47) and a toxin-positive group (n=67). Their general data and results of laboratory tests were compared between the two groups. SPSS Statistics 25.0 was used for statistical analysis. Based on data types, independent sample t test, rank sum test or Chi-square test was employed for comparison between groups. Multivariate binary logistic regression analysis was applied to analyze the influencing factors of CDI. Results The patients from the negative group had significantly higher aspartate aminotransferase [29.0(22.0,49.0) vs 20.0(15.0,34.0) U/L], alanine aminotransferase [21.0(14.0,41.0) vs 16.0(8.0,20.0) U/L], albumin [(33.22±4.94) vs (31.53±3.49) g/L], alkaline phosphatase [113.0 (69.0,163.0) vs 74.0 (56.0,101.0) U/L] and γ-glutamyl transpeptidase [64.0 (23.0,157.0) vs 35.0 (22.0,76.0) U/L], and obviously longer thrombin time [18.6(17.6,20.4) vs 17.8(16.7,18.9) s] when compared with the patients of the positive group (all P<0.05). Lower incidence of coronary heart disease [8(17.0%) vs 32(47.8%)] and usage ratios of proton pump inhibitor [16(34.0%) vs 42(62.7%)] and antibiotics [9(19.1%) vs 39(58.2%)] were observed in negative group than positive group (all P<0.05). Multivariate binary logistic regression analysis showed that albumin level was a protective factor for CDI (OR=0.894,95%CI 0.802-0.996; P=0.041), while use of antibiotics was an independent risk factor for CDI (OR=18.398,95%CI 1.225-276.346; P=0.035). Conclusion The incidence of CDI is negatively correlated with albumin level, and positively with use of antibiotics in the elderly inpatients. Because antibiotic use increases the incidence of CDI, dynamic monitoring and timely intervention should be implemented for the elderly hospitalized patients.