BACKGROUND Recent studies have reported that zeta-chain-associated protein kinase 70 (ZAP-70) expression plays a prognostic role in chronic lymphocytic leukemia (CLL). However, these results remain controversial. Thus, we performed a meta-analysis to clarify the prognostic value of ZAP-70 expression in CLL. METHODS Relevant studies were searched in PubMed, Embase, Cochrane library, and Web of Science up to January 2018. Clinicopathological features and prognostic data were extracted from the studies. We pooled estimates and 95% confidence intervals (CIs) and estimated the heterogeneity of studies using Mantel-Haenszel or DerSimonian and Laird method. RESULTS Twelve studies that included 1956 patients with CLL were eligible for inclusion. The pooled results revealed that increased ZAP-70 expression was significantly associated with poor overall survival (hazard ratio [HR] = 2.48, 95% CI: 1.72-3.59, P = 0.019, I2 = 53.0%) and event-free survival (HR = 4.17, 95% CI: 2.17-8.01, P = 0.014, I2 = 68.2%) in a random-effects model with significant heterogeneity. Clinicopathological analysis demonstrated that ZAP-70 expression was significantly associated with unmutated immunoglobulin heavy-chain genes, CD38 expression, serum β-2 microglobulin, and lymphocyte doubling time. CONCLUSIONS Our findings indicated that ZAP-70 was a strong prognostic biomarker for patients with CLL.