Objective: To study the epidemiology of serious infections in patients hospitalized with gout. Methods: We identified patients with gout hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), or opportunistic infections (OIs) in a US National Inpatient Sample from 1998 to 2016 and examined factors associated with utilization and mortality. Results: We noted 1,140,085 hospitalizations of patients with serious infections and gout (11% of all hospitalizations of patients with gout; 1998–2000 [8.9%], 2015–2016 [14.5%]). Compared to patients without gout, patients with gout hospitalized with serious infections were older (median age 65 versus 74 years), more of them had a Charlson–Deyo comorbidity index score ≥2 (42% versus 65%), and fewer were female (53% versus 35%) or non-White (40% versus 35%), respectively. The most common infection was pneumonia (52%) in 1998–2000 and sepsis (52%) in 2015–2016. Median hospital charges and hospital stays were higher for patients with sepsis and OIs in 2015–2016 ($41,000–$42,000; 5.1–5.5 days) versus those with UTI, pneumonia, or SSTIs ($15,000–$17,000; 3.0–3.9 days). Compared to patients with sepsis, the multivariable-adjusted odds of health care utilization and in-hospital mortality were significantly lower for patients with UTI, SSTIs, and pneumonia, and non-home discharge or in-hospital mortality were lower in patients with OIs. Among patients hospitalized with infections, older age, Medicaid coverage, a higher Charlson–Deyo comorbidity index score, Black race, and Northeast and nonrural hospital location were associated with significantly higher health care utilization and mortality, while female sex, Medicare insurance, and lower income were associated with higher utilization. Conclusion: Given an increasing rate of serious infections, especially sepsis and pneumonia, in individuals with gout, development of effective interventions targeting factors associated with health care utilization and mortality will improve outcomes and reduce burden.