Abstract Introduction Pericardial effusion (PE) is a complication of neoplastic processes that worsens the prognosis and can lead to symptomatic presentations requiring pericardiocentesis (PC). There is limited literature regarding the evolution of PE from its onset to the need for PC, characteristics of these patients, progression rate of PE, and potential accelerating factors. Purpose This study aims to: i) Analyze the baseline characteristics of patients undergoing PC; ii) Evaluate the correlation between PE appearance and cytology; iii) Analyze the progression rate until PC performance. Methods This retrospective observational study includes patients with active neoplasia and significant symptomatic PE treated with PC at our hospital from 01/01/2010 to 06/30/23, with subsequent follow-up until 10/31/23. Clinical characteristics related to neoplastic processes and PE diagnosis were analyzed, including PE appearance, cytology, and computed tomography scans performed as neoplasia follow-up prior to PC. Results A total of 75 patients were included, with 6 excluded because of non-malignant conditions (2 acute pericarditis-related PE, 3 purulent PE, and 1 chylous PE). The remaining 69 patients had a median age of 59 years, with 55.1% being male. Lung neoplasm was most frequent (63.8%, with 84% adenocarcinoma), followed by lymphomas/lymphoid leukemia (7.3%), upper digestive tract (7.3%), and breast cancer (7.3%). 52.2% of PEs undergoing PC were diagnosed simultaneously with neoplasm (70.45% associated with pulmonary neoplasms); 43.5% had ECOG 1, and 89.9% had metastases (excluding PE) at PC. Cardiac tamponade was present in 27.5%, with percutaneous pericardiostomy added in 21.7%. PE appearance was sero-haematic in 49.3%, haematic in 36.2%, and serous in 14.5%. Cytology showed mostly positive results (69.2%: 50% in serous PE and 71.93% in haematic/sero-haematic PE). The median time from the last CT scan prior to PE to PC was 5 months (160 days, range: 24-943 days). PC recurrence was observed in 30.4% of cases. Follow-up mortality was 82.6%, higher in breast, renal, digestive, thymoma, and genital neoplasms (100%), with hematological neoplasms having the lowest mortality (40%), followed by pulmonary neoplasms (79.5%). Mortality was higher in patients with more lines of treatment at PC and with a higher number of metastases. The median time from PC to death was 2 months (68.5 days, range: 1 day-2007 days). Conclusions The most common neoplastic PE was associated with lung adenocarcinoma, though a variety of neoplasms were observed. Half of PEs were diagnosed concurrently with neoplasm diagnosis. Cytology sensitivity was not high, and PE appearance did not adequately predict outcomes. The median time from the last CT scan prior to PE to PC was 5 months, potentially guiding echocardiographic follow-up once PE is observed on CT. Overall mortality was high (82.6%), except for onco-hematological PE.Iconographic summary of malignant PE