Objective Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic ischemic stroke or transient ischemic attack has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta‐analytical approach. Methods We performed a systematic literature review to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD, or both compared to the gold standard of TEE. Results Our literature search identified 35 eligible studies including 3,067 patients. The pooled sensitivity and specificity for TCD was 96.1% (95% confidence interval CI = 93.0–97.8%) and 92.4% (95% CI = 85.5–96.1%), whereas the respective measures for TTE were 45.1% (95% CI = 30.8–60.3%) and 99.6% (95% CI = 96.5–99.9%). TTE was superior in terms of higher positive likelihood ratio values (LR+ = 106.61, 95% CI = 15.09–753.30 for TTE vs LR+ = 12.62, 95% CI = 6.52–24.43 for TCD; p = 0.043), whereas TCD demonstrated lower negative likelihood values (LR− = 0.04, 95% CI = 0.02–0.08) compared to TTE (LR− = 0.55, 95% CI = 0.42–0.72; p < 0.001). Finally, the area under the summary receiver operating curve (AUC) was significantly greater (p < 0.001) in TCD (AUC = 0.98, 95% CI = 0.97–0.99) compared to TTE studies (AUC = 0.86, 95% CI = 0.82–0.89). Interpretation TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE. Ann Neurol 2016;79:625–635