Pneumococcal disease is a major cause of clinical and economic burden worldwide. This study investigated the burden of pneumococcal disease in Swedish adults. A retrospective population-based study was conducted using Swedish national registers, including all adults aged ≥18 years with a diagnosis of pneumococcal disease (defined as pneumococcal pneumonia, meningitis, or septicemia) in inpatient or outpatient specialist care between 2015–2019. Incidence and 30-day case fatality rates, healthcare resource utilization, and costs were estimated. Results were stratified by age (18–64, 65–74, and ≥75 years) and the presence of medical risk factors. A total of 10,391 infections among 9,619 adults were identified. Medical factors associated with higher risk for pneumococcal disease were present in 53% of patients. These factors were associated with increased pneumococcal disease incidence in the youngest cohort. In the cohort aged 65–74 years, having a very high risk for pneumococcal disease was not associated with an increased incidence. Pneumococcal disease incidence was estimated at 12.3 (18–64), 52.1 (64–74), and 85.3 (≥75) per 100,000 population. The 30-day case fatality rate increased with age (18–64: 2.2%, 65–74: 5.4%, ≥75: 11.7%), and was highest among septicemia patients aged ≥75 (21.4%). The 30-day average number of hospitalizations was 1.13 (18–64), 1.24 (64–74) and 1.31 (≥75). The average 30-day cost/infection was estimated at €4,467 (18–64), €5,278 (65–74), and €5,898 (≥75). The 30-day total direct cost of pneumococcal disease between 2015–2019 was €54.2 million, with 95% of costs from hospitalizations. The clinical and economic burden of pneumococcal disease in adults was found to increase with age, with nearly all costs associated with pneumococcal disease from hospitalizations. The 30-day case fatality rate was highest in the oldest age group, though not negligible in the younger age groups. The findings of this study can inform the prioritization of pneumococcal disease prevention in adult and elderly populations.