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Design considerations for robustness with respect to variations and low-power operations typically impose contradictory design requirements. Low-power design techniques such as voltage scaling, dual- , etc., can have a large negative impact on parametric yield. In this paper, we propose a novel paradigm for low-power variation-tolerant circuit design called critical path isolation for timing adaptiveness (CRISTA), which allows aggressive voltage scaling. The principal idea includes the following: 1) isolate and predict the set of possible paths that may become critical under process variations; 2) ensure that they are activated rarely; and 3) avoid possible delay failures in the critical paths by dynamically switching to two-cycle operation (assuming all standard operations are single cycle), when they are activated. This allows us to operate the circuit at reduced supply voltage while achieving the required yield. Simulation results on a set of benchmark circuits with Berkeley-predictive-technology-model [BPTM 70 nm: Berkeley predictive technology model] 70-nm devices that show an average of 60% improvement in power with small overhead in performance and 18% overhead in die area compared to conventional design. We also present two applications of the proposed methodology that include the following: 1) pipeline design for low power and 2) temperature-adaptive circuit design.