System-on-chip design is becoming increasingly complex as technology scaling enables more and more functionality on a chip. This scaling-driven complexity has resulted in a variety of reliability and validation challenges including logic bugs, hot spots, wear-out, and soft errors. To make matters worse, as we reach the limits of Dennard scaling, efforts to improve system performance and energy efficiency have resulted in the integration of a wide variety of complex hardware accelerators in SoCs. Thus the challenge is to design complex, custom hardware that is efficient, but also correct and reliable. High-level synthesis shows promise to address the problem of complex hardware design by providing a bridge from the high-productivity software domain to the hardware design process. Much research has been done on high-level synthesis efficiency optimizations. This dissertation shows that high-level synthesis also has the power to address validation and reliability challenges through three automated solutions targeting three key stages in the hardware design and use cycle: pre-silicon debugging, post-silicon validation, and post-deployment error detection. Our solution for rapid pre-silicon debugging of accelerator designs is hybrid tracing: comparing a datapath-level trace of hardware execution with a reference software implementation at a fine temporal and spatial granularity to detect logic bugs. An integrated backtrace process delivers source-code meaning to the hardware designer, pinpointing the location of bug activation and providing a strong hint for potential bug fixes. Experimental results show that we are able to detect and aid in localization of logic bugs from both C/C++ specifications as well as the high-level synthesis engine itself. A variation of this solution tailored for rapid post-silicon validation of accelerator designs is hybrid hashing: inserting signature generation logic in a hardware design to create a heavily compressed signature stream that captures the internal behavior of the design at a fine temporal and spatial granularity for comparison with a reference set of signatures generated by high-level simulation to detect bugs. Using hybrid hashing, we demonstrate an improvement in error detection latency (time elapsed from when a bug is activated to when it manifests as an observable failure) of two orders of magnitude and a threefold improvement in bug coverage compared to traditional post-silicon validation techniques. Hybrid hashing also uncovered previously unknown bugs in the CHStone benchmark suite, which is widely used by the HLS community. Hybrid hashing incurs less than 10% area overhead for the accelerator it validates with negligible performance impact, and we also introduce techniques to minimize any possible intrusiveness introduced by hybrid hashing. Finally, our solution for post-deployment error detection is modulo-3 shadow datapaths: performing lightweight shadow computations in modulo-3 space for each main computation. We leverage the binding and scheduling… Advisors/Committee Members: Chen, Deming (advisor), Chen, Deming (Committee Chair), Hwu, Wen-Mei W (committee member), Wong, Martin D F (committee member), Kim, Nam Sung (committee member).