The increasing system complexity of FPGA-based hardware designs and shortening of time-to-market have motivated the adoption of new designing methodologies focused on addressing the current need for high-performance circuits. High-Level Synthesis (HLS) tools can generate Register Transfer Level (RTL) designs from high-level software programming languages. These tools have evolved significantly in recent years, providing optimized RTL designs, which can serve the needs of safety-critical applications that require both high performance and high reliability levels. However, a reliability evaluation of HLS-based designs under soft errors has not yet been presented. In this work, the trade-offs of different HLS-based designs in terms of reliability, resource utilization, and performance are investigated by analyzing their behavior under soft errors and comparing them to a standard processor-based implementation in an SRAM-based FPGA. Results obtained from fault injection campaigns and radiation experiments show that it is possible to increase the performance of a processor-based system up to 5,000 times by changing its architecture with a small impact in the cross section (increasing up to 8 times), and still increasing the Mean Workload Between Failures (MWBF) of the system.