Automotive applications are driving the need for better IC quality, reliability, and functional safety, in a market that is cost-sensitive and rapidly changing. The goals are to deliver zero defective parts without time-consuming and expensive burn-in, and satisfy functional safety requirements. This paper shows how measuring the percentage of circuit elements that are subject to sufficient stress during testing, especially across thin oxides, can be used as a criterion to drive improving the circuit’s reliability. The paper also shows how to more accurately compute a circuit’s ISO 26262 metrics using activity-based defect likelihoods. Simulation results are provided for an ITC’17 mixed-signal benchmark circuit (bandgap + LDO + voltage monitor) and for an industrial automotive product IC, showing the potential of the method to improve reliability and functional safety of analog/mixed-signal ICs.