Hospitalized salmonellosis patients with concurrent chronic conditions may be at increased risk for adverse outcomes, increasing the costs associated with hospitalization. Identifying important modifiable risk factors for this predominantly foodborne illness may assist hospitals, physicians, and public health authorities to improve management of these patients. The objectives of this study were to (1) quantify the burden of salmonellosis hospitalizations in the United States, (2) describe hospitalization characteristics among salmonellosis patients with concurrent chronic conditions, and (3) examine the relationships between salmonellosis and comorbidities by four hospital-related outcomes. A retrospective analysis of salmonellosis discharges was conducted using the Agency for Healthcare Research and Quality's Nationwide Inpatient Sample for 2011. A supplemental trend analysis was performed for the period 2000-2011. Hospitalization characteristics were examined using multivariable regression modeling, with a focus on four outcome measures: in-hospital death, total amount billed by hospitals for services, length of stay, and disease severity. In 2011, there were 11,032 total salmonellosis diagnoses; 7496 were listed as the primary diagnosis, with 86 deaths (case-fatality rate = 1.2%). Multivariable regression analyses revealed a greater number of chronic conditions (≥4) among salmonellosis patients was associated with higher mean total amount billed by hospitals for services, longer length of stay, and greater disease severity (p ≤ 0.05). From 2000 to 2011, hospital discharges for salmonellosis increased by 27.2%, and the mean total amount billed by hospitals increased nearly threefold: $9,777 (2000) to $29,690 (2011). Observed increases in hospitalizations indicate the burden of salmonellosis remains substantial in the United States. The positive association between increased number of chronic conditions and the four hospital-related outcomes affirms the need for continual healthcare and public health investments to prevent and control this disease in vulnerable groups.