The strengths of our study include a comprehensive literature search with well-defined inclusion criteria and multiple subgroup analyses, with no subgroup analysis showing an increased risk of CDI with the use of tetracyclines. Limitations of our meta-analysis include that the individual studies varied in several ways, including study design, patient population (age, sex, inpatient vs outpatient status), method of CDI diagnosis, time period for prior antibiotic exposure, and dose and duration of tetracycline use. These variations led to substantial heterogeneity. Although all the studies controlled for some potential confounders, each individual study controlled for different variables. Hence, we were unable to perform analyses in which all confounding factors could be accounted or controlled for, including duration of exposure and dose of tetracyclines, indication for tetracycline use, adherence to infection-control practices, use of administrative diagnosis codes, and the possibility that a positive stool assay represented colonization rather than active infection. None of the studies included outpatients only; hence, we could not perform analyses separating inpatients vs outpatients only. We also could not perform analyses separating patients with hospital-acquired vs community-acquired CDI. All studies assessed the risk of primary CDI and excluded patients with recurrent CDI.