The aim of this study is to assess the clinical outcome of gemcitabine (GEM) plus molecular targeted agents (MTAs) for treatment of pancreatic cancer, in the purpose of providing fundamental data for clinical practice. Databases like PubMed, EMBASE, and MEDLINE, EMBASE and Cochrane Library were searched to retrieve phase III clinical randomized controlled trials related to GEM plus MTAs for pancreatic cancer (up to Oct 2013). Literatures were independently screened by two researchers according to the inclusion and exclusion criteria. Data were extracted and analyzed by using Stata 11.0 software. Total, 11 studies were included, involving 5,451 participants who were divided into GEM plus MTAs group (n=2,729) and GEM plus placebo group (n=2,722). There was no significant difference in overall survival, progression-free survival, response rate, complete response, partial response, and clinical benefit rate between two groups. Compared with GEM plus placebo group, stable disease of GEM plus MTAs group was significantly increased (risk ratios (RRs) =1.14, 95% confidence interval (CI) 1.04-1.21, P=0.003). Further subgroup analysis indicated that GEM plus epidermal growth factor receptor (EGFR) inhibitor use induced higher response rate and clinical benefit rate than GEM plus placebo group (RRs=1.19, 95% CI 1.09-1.31, P=0.000; RR=1.18, 95% CI 1.09-1.27, P=0.000). In addition, no significant difference in 3-4 grade adverse reactions (incidence, anemia rate, neutropenia rate, and thrombocytopenia rate) was identified between two groups. GEM plus MTAs may be effective and safe for stabilizing patients suffering advanced pancreatic cancer, especially EGFR inhibitor.