Background-Tissue Doppler index E/e' is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied. Methods and Results-From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/e' and invasive LVFP in preserved EF (≥50%). In random-effects models, E/e' had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography-recommended E/e' cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9-48%), 37% (13-61%), and 24% (6-46%), and summary specificity was 92% (82-100%), 91% (80-99%), and 98% (92-100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/e'. LR+ was slightly >10 for septal E/e' obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/e' (lateral, mean, and septal, respectively) was 64% (38-86%), 36% (3-74%), and 50% (14-81%), while summary specificity was 73% (54-89%), 83% (49-100%), and 89% (66-100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/e' could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability. Conclusions-There is insufficient evidence to support that E/e' can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/e' to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well-designed prospective clinical trial.