Multiple studies have noticed that factors such as being treated with rituximab as well assplenectomy have a hindering effect on the vaccine-mediated protective immuneresponse against infectious diseases and natural infections. The goal of this study is toexplore the difference of association between rituximab-treated versus splenectomizedpatients on vaccine-mediated protection by using meta-analysis. The literature search inPubmed was conducted in March 2017 and eight eligible studies for the statisticalanalysis were found. The studies can be allocated to subgroups studies with rituximabtreated(n=4) and splenectomized patients (n=4). Between the subgroups,splenectomized (p-value = 0.0063) and rituximab-treated (p-value = 0.0239) patientsboth have a significant risk for not acquiring adequate vaccine-mediated immuneprotection, but the association is stronger in splenectomized patients compared torituximab-treated patients (mixed effects pooled splenectomy log OR [95% CI]: 4.30[1.86-9.87]; pooled rituximab log OR [95% Cl]: 3.57 [0.97 – 13.08]. The underliningcause for the results in both subgroups is suggested to be the absence, or depletion ofmemory B -cells, a condition which is present in both splenectomized and rituximabtreatedpatients.