Introduction: Necrotizing soft tissue infection (NSTI), a potentially life-threatening diagnosis, is often not immediately recognized by clinicians. Delays in diagnosis are associated with increased morbidity and mortality. We sought to summarize and compare the accuracy of physical exam, imaging, and Laboratory Risk Indicator of Necrotizing Fasciitis (LRINEC) Score used to confirm suspected NSTI in adult patients with skin and soft tissue infections. Methods: We searched Medline, Embase and 4 other databases from inception through November 2017. We included only English studies (randomized controlled trials, cohort and case-control studies) that reported the diagnostic accuracy of testing or LRINEC Score. Outcome was NSTI confirmed by surgery or histopathology. Two reviewers independently screened studies and extracted data. We assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Diagnostic accuracy summary estimates were obtained from the Hierarchical Summary Receiver Operating Characteristic model. Results: We included 21 studies (n=6,044) in the meta-analysis. Of physical exam signs, pooled sensitivity and specificity for fever (49.4% [95% CI: 41.4-57.5], 78.0% [95% CI: 52.2-92.0]), hemorrhagic bullae (30.8% [95% CI: 16.2-50.6], 94.2% [95% CI: 82.9-98.2]) and hypotension (20.8% [95% CI: 7.7-45.2], 97.9% [95% CI: 89.1-99.6]) were generated. Computed tomography (CT) had 88.5% [95% CI: 55.5-97.9] sensitivity and 93.3% [95% CI: 80.8-97.9] specificity, while plain radiography had 48.9% [95% CI: 24.9-73.4] sensitivity and 94.0% [95% CI: 63.8-99.3] specificity. Finally, LRINEC 6 (traditional threshold) had 67.5% [95% CI: 48.3-82.3] sensitivity and 86.7% [95% CI: 77.6-92.5] specificity, while a LRINEC 8 had 94.9% [95% CI: 89.4-97.6] specificity but 40.8% [95% CI: 28.6-54.2] sensitivity. Conclusion: The absence of any one physical exam feature (e.g. fever or hypotension) is not sufficient to rule-out NSTI. CT is superior to plain radiography. The LRINEC Score had poor sensitivity, suggesting that a low score is not sufficient to rule-out NSTI. For patients with suspected NSTI, further evaluation is warranted. While no single test is sensitive, patients with high-risk features should receive early surgical consultation for definitive diagnosis and management.