Abstract Introduction Acute pericarditis accounts for 5% of emergency room admissions for chest pain. First line treatment consists of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. Systemic corticosteroids (SCS) are usually reserved as a second-line therapy due to a higher rate of recurrences and side effects. Whether a short pulse of low-dose SCS is safe and effective during the acute phase of the disease remains unknown. Purpose To investigate safety and efficacy of a 3 day pulse of 40 mg intravenous methylprednisolone in patients hospitalized for acute pericarditis with a lack of response to NSAIDs and colchicine. Methods A retrospective, observational and unicentric study was performed including patients hospitalized for acute pericarditis between 2019 and 2023. Patients with asymptomatic pericardial effusion or predominance of myocardial injury were excluded. Patients were considered to be refractory to conventional treatment when at least one of the following criteria was present despite five days of high-dose NSAIDs and colchicine: 1- Moderate/severe pericardial effusion persistence. 2- Chest pain persistence. 3- Increase of inflammatory biomarkers. These patients received methylprednisolone 40mg for three days on top of standard treatment. Baseline characteristics, treatment received during hospitalization and events during follow-up were analysed. Data were expressed as mean and standard deviation (quantitative variables) and percentages (categorical variables). Two-sided P value of less than 0.05 was considered statistically significant. Results 70 patients with acute pericarditis requiring hospitalization were included (54±19 years; 71% male) with a mean follow-up of 10±21 months. 26 of them (37%) received methylprednisolone 40mg for three days due to lack of response to standard treatment. Table 1 includes a comparison of patients who received systemic corticosteroids versus those who did not (control group). C-reactive protein (CRP) was significantly higher in the group receiving corticosteroids (188±86 mg/L vs 135±85 mg/L; p=0.014) and it significantly decreased during hospital stay compared to the control group (151±87 mg/L vs 97±74 mg/L; p=0.013). 14 patients (20%) experienced a recurrence of chest pain during follow-up with no significant difference according to the treatment received (27% vs 16%; p=0.266) Conclusion A 3-day pulse of low-dose SCS seems to be useful and safe for hospitalized patients with acute pericarditis who show lack of response to NSAIDs and colchicine, with no increase in recurrence rate. However, more evidence based on randomized control trials is needed to support this therapeutic approach.Table 1