Early thrombolysis for individuals experiencing a myocardial infarction is associated with better mortality and morbidity outcomes. While traditionally thrombolysis is given in hospital, pre-hospital thrombolysis is proposed as an effective intervention to save time and reduce mortality and morbidity in individuals with ST-elevation myocardial infarction (STEMI). Despite some evidence that pre-hospital thrombolysis may be delivered safely, there is a paucity of controlled trial data to indicate whether the timing of delivery can be effective in reducing key clinical outcomes. To assess the morbidity and mortality of pre-hospital versus in-hospital thrombolysis for STEMI. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), two citation indexes on Web of Science (Thomson Reuters) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for randomised controlled trials and grey literature published up to June 2014. We also searched the reference lists of articles identified, clinical trial registries and unpublished thesis sources. We did not contact pharmaceutical companies for any relevant published or unpublished articles. We applied no language, date or publication restrictions. The Cochrane Heart Group conducted the primary electronic search. We included randomised controlled trials of pre-hospital versus in-hospital thrombolysis in adults with ST-elevation myocardial infarction diagnosed by a healthcare provider. Two authors independently screened eligible studies for inclusion and carried out data extraction and 'Risk of bias' assessments, resolving any disagreement by consulting a third author. We contacted authors of potentially suitable studies if we required missing or additional information. We collected efficacy and adverse effect data from the trials. We included three trials involving 538 participants. We found low quality of evidence indicating uncertainty whether pre-hopsital thrombolysis reduces all-cause mortality in individuals with STEMI compared to in-hospital thrombolysis (risk ratio 0.73, 95% confidence interval 0.37 to 1.41). We found high-quality evidence (two trials, 438 participants) that pre-hospital thrombolysis reduced the time to receipt of thrombolytic treatment compared with in-hospital thrombolysis. For adverse events, we found moderate-quality evidence that the occurrence of bleeding events was similar between participants receiving in-hospital or pre-hospital thrombolysis (two trials, 438 participants), and low-quality evidence that the occurrence of ventricular fibrillation (two trials, 178 participants), stroke (one trial, 78 participants) and allergic reactions (one trial, 100 participants) was also similar between participants receiving in-hospital or pre-hospital thrombolysis. We considered the included studies to have an overall unclear/high risk of bias. Pre-hospital thrombolysis reduces time to treatment, based on studies conducted in higher income countries. In settings where it can be safely and correctly administered by trained staff, pre-hospital thrombolysis may be an appropriate intervention. Pre-hospital thrombolysis has the potential to reduce the burden of STEMI in lower- and middle-income countries, especially in individuals who have limited access to in-hospital thrombolysis or percutaneous coronary interventions. We found no randomised controlled trials evaluating the efficacy of pre-hospital thrombolysis for STEMI in lower- and middle-income countries. Large high-quality multicentre randomised controlled trials implemented in resource-constrained countries will provide additional evidence for the efficacy and safety of this intervention. Local policy makers should consider their local health infrastructure and population distribution needs. These considerations should be taken into account when developing clinical guidelines for pre-hospital thrombolysis.