An important health problem affecting approximately 30% of women is heavy menstrual bleeding, which has a major effect on their quality of life. A frequently used minimally invasive procedure that can destroy or remove the endometrial tissue is endometrial ablation (EA). Because EA is less invasive than hysterectomy and has a shorter recovery period, it has become an alternative to hysterectomy for the treatment of heavy menstrual bleeding.The many techniques available to remove the endometrial tissue include first-generation techniques (which require visualization of the uterine cavity with a hysteroscope during the procedure) and second-generation techniques (which are other than from hydrothermal ablation) nonhysteroscopic, disposable devices. Second-generation devices are at least as effective as first-generation devices, require fewer surgical skills, have a shorter operative time, and fewer complications. In addition, they can be performed in an outpatient setting. Second-generation ablation techniques used in daily practice include bipolar radiofrequency, microwave, thermal balloon, endometrial cryotherapy, and hydrothermal ablation. Satisfaction rates with these procedures are high, approximately 80% to 90%. However, approximately 10% to 20% of women undergoing EA do not respond to treatment and require additional surgery (reablation or hysterectomy) in large part because of persistent pain or bleeding. Many prognostic factors have been investigated with the aim to identify and predict which women are at risk of failure of EA.The aim of this systematic review is to provide an overview of prognostic factors predicting failure of second-generation EA. A search of the electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov was conducted from 1988 until February 11, 2019, to identify relevant articles. There were no language restrictions, and the following search terms were used: "endometrial ablation," "prognosis," "predict," "long term," "late onset," and "outcome." All studies with original data about prognostic factors for EA failure were included.After removing duplicates, the initial search identified 990 studies. A total of 213 full-text studies were screened for eligibility. Among the 56 studies meeting inclusion criteria, 21 cohort studies and case-control studies provided results that could be included in the meta-analysis. The following 10 potential prognostic factors selected were clinically relevant factors most often investigated in the included studies: age, myomas, tubal ligation before EA (no concurrent intervention), body mass index, parity, preexisting dysmenorrhea, cesarean delivery, bleeding pattern, uterus position, and uterus length.The primary study outcome was surgical reintervention (reablation or hysterectomy), and meta-analysis was performed to estimate summary treatment effects. Increased risk of surgical reintervention was associated with younger age (35 years or younger: odds ratio [OR], 1.68; 95% confidence interval [CI], 1.19-2.36; 40 years or younger: OR, 1.58; 95% CI,1.30-1.93; 45 years or younger: OR, 1.63; 95% CI, 1.28-2.07), prior tubal ligation (OR, 1.46; 95% CI, 1.23-1.73), and preexisting dysmenorrhea (OR, 2.12; 95% CI, 1.41-3.19). Conflicting results were found in studies investigating the potential prognostic factors myomas and obesity.In summary, 3 prognostic factors (younger age, history of tubal ligation, and preexisting dysmenorrhea) were associated with failure of EA. Other risk factors for EA failure may be obesity and the presence of large submucous myomas. More robust data from future studies are needed to estimate the influence of these 2 factors. Women with heavy menstrual bleeding opting for EA who have 1 or more of these prognostic factors could be informed about the higher risk of failure. With additional data, prediction models based on prognostic factors could be developed to guide choice of ablation methods.