Background To investigate the incidence and risk of cardiac toxicities between dual HER-2 blockade and anti-HER-2 monotherapy. Materials and methods We searched PubMed, EMBASE and Cochrane library databases to identify relevant trials between January 1 1990 and October 31 2019. Statistical analyses were conducted to calculate the summary incidence, Petro odds radio (Peto ORs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models. Results A total of 16,375 patients from 15 randomized controlled trials were included for analysis; the pooled incidence of LVEF decline and CHF in dual HER-2 blocked were 4.6% and 0.9%, which was higher than that in anti-HER-2 monotherapy (3.2% and 0.7%, respectively). Dual HER-2 blockade therapy in breast cancer patients significantly increased the risk of developing LVEF decline (OR:1.19, 95%CI: 1.02-1.40, p=0.031) and CHF (OR:1.45, 95%CI: 1.00-2.11, p=0.049) when compared to anti-HER2 monotherapy. Sub-group analysis showed that addition of dual HER-2 blockade to adjuvant treatment for breast cancer significantly increased the risk of developing LVEF decline (p=0.048) and CHF (p=0.005). In addition, dual HER-2 blockade in breast cancer patients significantly increased the risk of developing LVEF decline (p=0.004) when compared to lapatinib alone, but not for CHF (p=0.11, respectively). Conclusion Dual HER-2 targeted therapy in HER-2 positive breast cancer significantly increase the risk of developing LVEF and CHF when compared to anti-HER-2 alone, though the overall incidence of cardiac toxicities is very low. Physicians should be aware of this risk and provide close monitoring during the administration of dual HER-2 targeted therapy.