To be a high-reliability organization, organizations need to continually assess risks and predict potential failures before even they actually occur. In this paper, we present a new method to uncover and assess risks and failures embedded in a work system: systems ambiguity framework. We define systems ambiguity as uncertainty or vagueness that may prevent a work system from achieving its purpose. We identified five main types of ambiguity in a work system: task ambiguity, responsibility ambiguity, expectation ambiguity, method ambiguity, and exception ambiguity. Examples for each type of ambiguity are provided from a qualitative study aimed at identifying the underlying causes of non-compliance to evidence based guidelines in intensive care units. We argue that systems ambiguity framework can be used alone or in conjunction with well-known risk assessment methods (e.g., root cause analysis, failure modes and effects analysis) to uncover systems failures both reactively and proactively.