Background: As the cause of the majority of nosocomial diarrhea in industrialized nations, Clostridium difficile infection is a significant public health threat. Over the past decade incidence of both hospital- and community-acquired C. difficile-associated diarrhea (CDAD) has increased, as have case morbidity and mortality. The mechanism of action of prescription acid suppression medications makes it a plausible candidate as a risk factor for increased morbidity and mortality among individuals with CDAD. Acid suppression has been suggested as a risk factor for C. difficile infection. Studies have also shown an association between acid suppression use and recurrent C. difficile infection. Increased age is an established risk factor for morbidity and mortality related to CDAD, the oldest old are particularly considered to be at risk for increased complications. Purpose: A retrospective study of patients diagnosed with CDAD was performed to determine the prevalence of complications with CDAD, and to examine factors associated with complications. We hypothesized that complications would be positively associated with patients being older than 80 years, and with use of acid suppression medications. Methods: Demographic, clinical and medication use data were obtained from medical and pharmacy records of patients diagnosed with CDAD between November 2004 and November 2008 at Naval Medical Center San Diego. Following univariable analysis, a multivariable logistic regression model was fitted using stepwise elimination of variables to evaluate risk factors associated with complications of CDAD. Results: 472 cases were included, 62% were inpatients and 38% outpatients. The study population had a median age of 52.5 years and was 53% male. 55 (12%) patients with CDAD had at least one complication, 22 (5%) died. All of the patients with complications were inpatient. Acid suppression use, age ?80 years, and admission for CDAD (compared to admission for a different reason) were found to be independently associated with complications of CDAD (OR 2.96 p=0.0009, OR 2.79 p=0.007, OR 4.91 p<0.0001 respectively). Conclusions: Considering the common usage of acid suppression medication, this finding has important public health implications. Physicians prescribing acid suppression should ensure use of the lowest effective dose. Strict adherence to universal precautions and barrier methods of infection control must be taken around hospital inpatients on acid suppression medication, and the elderly, to reduce exposure to C. difficile spores. In addition, careful observation and aggressive treatment of patients admitted specifically for CDAD may be warranted. Further studies of the impact of acid suppression on outcomes of CDAD are needed.