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BACKGROUND: The severity of pulmonary embolism (PE) after isolated calf deep vein thrombosis (C-DVT) is controversial, which leads to inconsistent clinical decision making when treating C-DVT. This systematic review assessed PE frequency and severity in patients with C-DVT. METHODS: Database searches were completed using MEDLINE and Scopus along with cross-referencing. Two independent reviewers used using rigorous inclusion and exclusion criteria to screen the papers. Data concerning PE and C-DVT characteristics as well as methods of detection were abstracted. Studies reporting combined outcomes for patients with proximal and C-DVT, those with concurrent PE at diagnosis, and retrospective studies not allowing the determination of C-DVT and PE as separate events were excluded. RESULTS: Of 586 papers that were screened, 21 met inclusion criteria, which included eight randomized clinical trials and 13 prospective cohort studies. There was data heterogeneity among patients, methods of diagnosis, and follow-up. PE diagnosis was often based on ventilation/perfusion scanning, where more recent studies used computed tomography angiography. The PE is usually overestimated because it includes concurrent events. The incidence of PE from isolated C-DVT in our review was 0% to 6.2%. No fatal PEs were reported. No data were found on PE severity and patient outcomes regarding this complication. CONCLUSIONS: Reported adverse outcomes of PE from C-DVT are infrequent, and clinical severity is unclear. Further studies are necessary to determine the actual risk associated with PE after C-DVT to establish proper treatment.