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This paper presents a flow that is suitable to estimate energy dissipation of digital standard-cell based designs which are determined to operate in the subthreshold regime. The flow is applicable on gate-level netlists, where back-annotated toggle information is used to find the minimum energy operation point, corresponding maximum clock frequency, as well as the dissipated energy per clock cycle. The application of the model is demonstrated by exploring the energy efficiency of pipelining, retiming, and register balancing. Simulation results, which are obtained during a fraction of SPICE simulation time, are validated by measurements on a wavelet-based cardiac event detector that was fabricated in 65-nm low-leakage high-threshold technology. The mean of the absolute modeling error is calculated as 5.2%, with a standard deviation of 6.6% over the measurement points. The cardiac event detector dissipates 0.88 pJ/sample at a supply voltage of 320 mV.