Pulmonary embolism (PE) is a common and life-threatening condition. Misdiagnosis of PE is not uncommon as symptoms can overlap with other diagnoses and could cause potential harm. We conducted a systematic review to estimate rates of misdiagnosis and factors may be associated with misdiagnosis of PE. We searched MEDLINE and EMBASE for studies that evaluated the misdiagnosis of PE. The rate of misdiagnosis was pooled and results were narratively synthesized. A total of 18 studies were included which included 2,053 patients with a diagnosis of PE. Two different definitions were used for misdiagnosis of PE. The first refers to an initial diagnosis that is not PE and the patient is found to have PE. The second definition refers to patients who do not have a diagnosis of PE while they were alive and PE was subsequently found on autopsy. The pooled results across the studies suggest that in ED settings 27.5% of patients with PE are misdiagnosed initially and half of all patients in inpatient settings are misdiagnosed (53.6%). Among patients that die in intensive care who undergo autopsy 37.9% were found to have PE that was missed. The commonly diagnosed conditions instead of PE were respiratory infection, heart failure and acute coronary syndrome (ACS). Misdiagnosis in patients with an eventual diagnosis of PE is common. Clinicians should consider PE as differential diagnosis in patients who are initially suspected to have chest infection, heart failure or ACS who have negative diagnostic tests or poor response to treatment.