OBJECTIVES: Romiplostim and eltrombopag are thrombopoietin receptor (TPOr) agonists that promote megakaryocyte differentiation, proliferation and platelet production. Both are orphan drugs mainly indicated for the treatment of  adult chronic idiopathic thrombocytopenic splenectomised patients who are refractory to other treatments. Due to increasing platelet counts above the normal range may represent a risk for thromboembolisms, we assessed whether TPOr agonists affect thromboembolisms occurrence by a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: We searched PubMed, SCOPUS, Cochrane Central Register, regulatory agencies websites and publicly available registries of manufacturers (before January 2011). RCTs using romiplostim or eltrombopag in at least one group were included. Absolute risk ratios (ARR) and number needed to harm (NNH) were calculated to provide the population health impact of the exposure. Relative risks (RR) were also provided. Data were pooled using fixed-effects models. Heterogeneity was analysed using Cochran’s Q and I2 tests. RESULTS: Of 373 publications identified, 8 studies met the inclusion criteria (n=1,180 patients). In the TPOr agonist group, as compared with the control group (e.g. placebo and/or standard of care), the meta-ARR for thromboembolisms was 1.8% (95% CI, 0.0% to 3.6%), and the meta-RR was 1.5 (95% CI, 0.7 to 3.3). Fifty-five patients would have to be treated using TPOr agonists to produce thromboembolisms in a patient (meta-NNH=55). Non heterogeneity was found (Cochran's Q test, P = 0.9; I2 = 0.0%). CONCLUSIONS: Although the small numbers reported, thromboembolisms should be considered as identified risks for these drugs. Healthcare providers should use caution when administering these agents to patients with known risk factors for thromboembolisms.