Objective: To assess the effectiveness of subxiphoid pericardiostomy in the treatment and diagnosis of pericardial effusions. Methods: 368 patients who underwent subxiphoid pericardiostomy and tube drainage for cardiac tamponade, moderate to severe pericardial effusion, or suspicious bacterial aetiology were retrospectively analysed. Biopsies of the pericardium and fluid samples for diagnostic tests were obtained from each patient. Results: The mean age of the patients was 38.4 years, and the male to female ratio was 220:148. The pericardial effusion was classified by echocardiography as severe in 53% of the patients, moderate in 43%, and mild in 4%. The incidence of cardiac tamponade was 25%. Myocardial injury requiring sternotomy occurred as an operative complication in 0.8% of the patients and recurrent effusion necessitating further surgical intervention developed in 10% of patients. Histopathological examination and the polymerase chain reaction of specimens of pericardium and fluid were helpful for establishing a diagnosis in 90% of patients with malignancy and 92% of patients with tuberculous pericarditis. The overall 30 day mortality rate was 0.8%. Patients were followed up for at least one year. Pericardial constriction requiring pericardiectomy developed in 3% of the patients. Conclusions: Pericardial effusions of various causes can be safely, effectively, and quickly managed with subxiphoid pericardiostomy in both adults and children.