We present bacterial 16S rRNA gene datasets derived from stool samples of 44 patients with diarrhea indicative of a Clostridioides difficile infection. For 20 of these patients, C. difficile infection was confirmed by clinical evidence. Stool samples from patients originating from Germany, Ghana, and Indonesia were taken and subjected to DNA isolation. DNA isolations of stool samples from 35 asymptomatic control individuals were performed. The bacterial community structure was assessed by 16S rRNA gene analysis (V3-V4 region). Metadata from patients and control individuals include gender, age, country, presence of diarrhea, concomitant diseases, and results of microbiological tests to diagnose C. difficile presence. We provide initial data analysis and a dataset overview. After processing of paired-end sequencing data, reads were merged, quality-filtered, primer sequences removed, reads truncated to 400 bp and dereplicated. Singletons were removed and sequences were sorted by cluster size, clustered at 97% sequence similarity and chimeric sequences were discarded. Taxonomy to each operational taxonomic unit was assigned by BLASTn searches against Silva database 123.1 and a table was constructed.