Remotely Piloted Aircraft Systems (RPAS) are becoming more and more popular with an increasing number of companies using them in the fields of precision agriculture, emergency delivery of medical aid and preventive maintenance. Trials are being made to extend their use to public safety, monitoring traffic, providing internet and even air taxi services. These RPAS operations are currently handled on a case-by-case basis and operated in segregated airspace by creating temporary restricted areas for other traffic. With the SESAR Joint Undertaking (SJU) estimating that in the next 30 years 20% of the traffic will be remotely piloted, the option of airspace segregation will no longer be feasible. Therefore, integrating RPAS with current manned operations will be required. In doing so, however, the current levels of safety and efficiency should not be compromised. The command and control link (C2), which connects the remotely piloted aircraft and the remote pilot station, plays a pivotal role in the controllability of the aircraft, ATC communication and conflict detection and avoidance systems (CD&A). This project, which is conducted between Delft University of Technology and EUROCONTROL, aims at establishing a methodology of determining how different percentages of flights that are remotely piloted and different C2 link failure rates influence the number of separation losses (blind encounters). For this, fast time simulations of a 24-hour period of the Dutch airspace are performed in AirTOp. This study will contribute to the integration of RPAS in non-segregated airspace and will serve as an input for the regulatory bodies which are yet to set performance standards on RPAS, particularly the C2 link. Replacing between 10 - 50% of the flights in the Dutch airspace by RPAS with failure rates of the C2 link of 0.01 - 0.001 resulted in 1 - 15 flights being replaced by an RPAS with C2 link failure. This generated an additional number of blind encounters between 1.8 - 23.6, or an increase of 0.09 - 1.18% compared to the baseline situation (same traffic, no RPAS). Also, a linear relationship was found between the number of RPAS experiencing a failure of the C2 link and the number of blind encounters. The project also investigates how an RPAS that experiences a failure of the C2 link right at the moment when it enters an ATC sector in Langen FIR (EDGGPHHM) penalizes key ATM performance indicators. The considered KPIs are: number of potential conflicts, air traffic controller task load, sector occupancy, distance flown, flight time, fuel consumption and altitude deviation. The scope is limited to en-route operations above 500 ft and the contingency strategy followed by the RPAS once it loses the C2 link is to proceed to its destination along its originally submitted flight plan. At the same time, air traffic controllers would enforce a separation bubble around the RPAS, such that a buffer is created for the situations in which the remotely piloted aircraft might deviate from it route or behave erratically. Two RPAS performance models are considered: MQ-9 Reaper, a turboprop with a lower cruise speed and climb/descent performance than current civil aircraft and RQ-4A Global Hawk, a turbofan with a cruise speed close to that of civil aircraft and a rate of climb slightly higher. The results of the Monte Carlo tests are analyzed using ANOVA and MANOVA tests. Increasing the size of the separation bubble around the RPAS with C2 link failure by 20%, 40% and 60% resulted in an increase in the number of potential conflicts of 8.3%, 9.2% and 12.0% when a MQ-9 was used. The impact on controller task load was found to be small (increase of 0.4%) and not affected by the size of the separation bubble. Similarly the other KPIs were not affected by a separation increases of up to 60%. Switching 10-30% of the flights to RPAS and using even larger sizes of the separation bubble (twice or three times as large as the minimum ICAO standards) increased the number of potential conflicts by up to 72.9%, sector occupancy by 11.2% and the additional time spent in the sector by 1.4%. Based on the separation requirements which will be enforced around RPAS, the methodology used in the report can be used to assess the impact of experiencing a C2 link loss on the ATM environment.