Defenses against jailbreak attacks on Large Language Models (LLMs) operate at different pipeline stages, such as input modification or output guard, but it remains unclear which defenses to deploy at each stage and how to combine them. Prior empirical studies, fragmented by inconsistent attack-success-rate definitions and experimental settings, have evaluated defenses largely in isolation. Here we present the first systematic study, to our knowledge, of defense combinations both within and across pipeline stages, under a consistent threat model of direct, black-box, single-turn attacks. Our decision framework standardizes evaluation through a principled attack-success-rate formulation with controlled query budgets, together with explicit fairness rules. Across 19 attacks and 15 defenses, we find that no single defense is universally best, but well-chosen combinations achieve substantial safety with minimal utility degradation, yielding practical recommendations for layered defense pipelines.

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