Depression is common and associated with reduced quality of life (QoL) in people with epilepsy (PWE). Although multiple studies have investigated the relevant predictors, the results have been inconsistent. This meta-analysis aimed to investigate the risk factors that might increase the possibility of depression in this population. Medline, The Cochrane Library, Web of Science, and Embase were comprehensively searched for cross-sectional studies on the occurrence of depression in PWE. A random effects model was used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs). Heterogeneity between the study results and the probability of publication bias were also assessed. Fifty-one cross-sectional studies with sample sizes ranging from 36 to 1763 were included in this meta-analysis. The significant factors associated with an increased risk of depression were older age (odds ratio [OR]: 1.02, 95% CI: 1.00-1.04; p = 0.019), female gender (OR: 1.58, 95% CI: 1.30-1.93; p < 0.001), low education level (OR: 3.38, 95% CI: 2.86-4.00; p < 0.001), not being employed (OR: 1.61, 95% CI: 1.08-2.38; p = 0.019), poor antiepileptic drug (AED) adherence (OR: 2.84, 95% CI: 1.94-4.16; p < 0.001), polytherapy (OR: 2.25, 95% CI: 1.48-3.41; p < 0.001), stigma (OR: 2.22, 95% CI: 1.71-2.88; p < 0.001), and anxiety (OR: 2.21, 95% CI: 1.66-2.94; p < 0.001). A shorter epilepsy duration was significantly associated with a lower risk of depression (OR: 0.99, 95% CI: 0.99-0.99; p < 0.001), whereas marital status (OR: 1.07, 95% CI: 0.90-1.20; p = 0.684), economic level (OR: 1.01, 95% CI: 0.95-1.08; p = 0.684), age at seizure onset (OR: 0.99, 95% CI: 0.75-1.29; p = 0.912), and seizure control (OR: 1.03, 95% CI: 0.65-1.63; p = 0.900) did not increase the risk of depression. This meta-analysis defined several factors related to an increased risk of depression in PWE and can contribute to better prevention and screening strategies for depression in this group. The mechanisms behind this comorbidity remain to be further investigated to determine individually appropriate and targeted interventions. Copyright © 2020 Elsevier Inc. All rights reserved.