Background: In out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS’ urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking. Methods: We included data from adults (≥18 years) who contacted two large Dutch OHS-PC centres for SOB between 1 September 2020 and 31 August 2021 and whose follow-up data about final diagnosis could be retrieved from their own general practitioner (GP). The diagnostic accuracy (sensitivity and specificity with corresponding 95% confidence intervals (CI)) of the NTS’ urgency levels (high (U1/U2) versus low (U3/U4/U5) and ‘final’ urgency levels (including overruling of the urgency by triage nurses or supervising general practitioners (GPs)) was determined with life-threatening events (LTEs) as the reference. LTEs included, amongst others, acute coronary syndrome, pulmonary embolism, acute heart failure and severe pneumonia. Results: Out of 2012 eligible triage calls, we could include 1833 adults with SOB who called the OHS-PC, mean age 53.3 (SD 21.5) years, 55.5% female, and 16.6% showed to have had a LTE. Most often severe COVID-19 infection (6.0%), acute heart failure (2.6%), severe COPD exacerbation (2.1%) or severe pneumonia (1.9%). The NTS urgency level had a sensitivity of 0.56 (95% CI 0.50–0.61) and specificity of 0.61 (95% CI 0.58–0.63). Overruling of the NTS’ urgency allocation by triage nurses and/or supervising GPs did not impact sensitivity (0.56 vs. 0.54, p = 0.458) but slightly improved specificity (0.61 vs. 0.65, p < 0.001). Conclusions: The semi-automatic decision support tool NTS performs poorly with respect to safety (sensitivity) and efficiency (specificity) of urgency allocation in adults calling Dutch OHS-PC with SOB. There is room for improvement of telephone triage in patients calling OHS-PC with ...