Introduction Intrapericardial fibrinolysis has been proposed as a means of preventing complications of pericardial effusion such as cardiac tamponade, persistent and recurrent pericardial effusion, and pericardial constriction. There is a need to understand the efficacy and safety of this procedure because it shows promise.

Methods and analysis We aim to assess the effects of intrapericardial fibrinolysis in the treatment of pericardial effusion. We will search PubMed, the Cochrane Library, African Journals online, Cumulative Index to Nursing and Allied Health Literature, Trip database, Clinical trials.gov and the WHO International Clinical Trials Registry Platform for studies that evaluate the efficacy and/or safety of complete pericardial fluid drainage by intrapericardial fibrinolysis irrespective of study design, geographical location, language, age of participants, aetiology of pericarditis or types of fibrinolytics. Two authors will do the search independently, screen the search outputs for potentially eligible studies and assess whether the studies meet the inclusion criteria. Discrepancies between the two authors will be resolved through discussion and arbitration by a third author. Data from the selected studies shall be extracted using a standardised data collection form which will be piloted before use. The methodological quality of studies will be assessed using the Cochrane Collaboration's tools for assessing risk of bias for experimental studies and non-randomised studies, respectively. The primary meta-analysis will use random effects models due to expected interstudy heterogeneity. Dichotomous data will be analysed using relative risk and continuous with data mean differences, both with 95% CIs.

Ethics and dissemination Approval by an ethics committee is not required for this study as it is a protocol for a systematic review of published studies. The results will be disseminated through a conference presentation and peer-reviewed publication.

Review registration number PROSPERO, CRD42014015238.