The forthcoming integration of Remotely Piloted Aircraft System (RPAS) is one of the cmost omplex challenges for aviation. Europe draws to allow operating RPAS and conventional aircraft in non-segregated airspace by 2025, but this demanding perspective entails a thorough analysis of the different aspects involved. The RPAS integration in non-segregated airspace cannot imply an increase in the safety levels. This paper assesses how the RPAS integration affects safety levels. The goal is to regulate the number of RPAS that can jointly operate with conventional aircraft regarding conflict risk. This approach benchmarks a Calculated Level of Safety (CLS) with a Target Level of Safety (TLS). Monte Carlo (MC) simulations quantify the TLS based on schedules of conventional aircraft. Then, different combinations of conventional aircraft and RPAS provide different CLS. MC simulations are performed based on probabilistic distributions of aircraft performances, entry times and geographical distribution of aircraft. The safety levels are based on a conflict-risk model because the primary metrics are average number of conflicts and average conflict duration. The methodology is applied to one flight level of en-route airspace. The results provide restrictions to the number of RPAS that can jointly operate with conventional aircraft. Particularly, the TLS is quantified for four conventional aircraft and MC simulations provide the combinations of conventional aircraft and RPAS that fulfil the CLS. The same number of RPAS than conventional aircraft shows an increase over 90% average number of conflicts and 300% average conflict time.