In network designs, the decision made when implementing dynamic routing protocols is very paramount to the speed of the network. To make the best choice of protocol to deploy, several decisions has to be considered. Usually, these decisions are made based on the performance of the routing protocol with respect to some quantitative parameters. The protocol that performs better than other protocols involved in a research is selected for routing purposes. In this research paper, performance comparison of two mixed protocols namely OSPFv3/IS-IS and RIPng/IS-IS in IPv6 network has been made. Their performances have been measured and comparison made by simulation using Riverbed Modeller Academic Edition. The objective of this paper is mainly to determine which of the mixed protocols will be more suitable to route traffic in IPv6 network. The main motivation for this paper is to find out if the difference in the routing algorithms of RIPng and IS-IS will offset and produce a better performance than a combination of two routing protocols of the same routing algorithm (thus OSPFv3 and IS-IS). To achieve this paper’s objective, the simulation was divided into two scenarios. The first scenario was an OSPFv3/IS-IS configured IPv6 network topology. The second scenario is a copy of the first scenario but configured with RIPng/IS-IS. The two scenarios were simulated and the effect of using each of the scenarios to separately route the selected applications was measured and recorded. The performance comparison of the mixed protocols was based on the following quantitative parameters: database query response time, database query traffics received, email upload/download response time, ftp upload/download response time, ftp traffic received, http page response time, remote login response timeandIPv6 traffics dropped. The results obtained from the simulation indicated that RIPng/IS-IS scenario performed better in email download/upload response time, remote login response time, IPv6 traffics dropped and remote login response time while the mixture of OSPFv3/IS-IS performed better in database query response time, database query traffics received, ftp download/upload response time, ftp traffic received and http page response time. Hence OSPFv3/IS-IS is the better option when the choice is between RIPng/IS-IS and OSPFv3/IS-IS for most of the quantitative parameters involved in this paper. This is because the combination of RIPng and IS-IS took a longer time to converge, affecting the speed on the network scenario. The time the RIPng/IS-IS combination took to access most of the application servers is slower than that of OSPFv3/IS-IS network scenario. On the basis of database query and ftp traffics received, the simulation results showed that network configured with OSPFv3/IS-IS performs better than RIPng/IS-IS. This is because the OSPFv3/IS-IS received the highest database and ftp traffics. The mixture of OSPFv3/IS-IS sent and received more application packets because it had very high throughput values which had an effect on the total quantity of application traffics received. Although the OSPFv3/IS-IS network scenario recorded the highest database and ftp traffics, this could not affect its speed to become lower than the RIPng/IS-IS scenario.