Background: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. Methods: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9 – April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Findings: Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P=0·006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1·95 (95% CI: 1·10–3·64), which increased to 2·61 (95% CI: 1·50–4·45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37·5°C (3·49 (95% CI: 1·95–6·21)), and those with myalgias (1·83 (95% CI: 1·04–3·23)). Anosmia/ageusia was reported less frequently (16%) than other symptoms by HCWs with positive assays, but associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR=7·21 (95% CI: 2·95–17·67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98·2% (95% CI: 96·8–99·0%) for the exclusion of clinically relevant COVID-19. Interpretation: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia and fever were the two strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays. Funding Statement: None. Declaration of Interests: None Ethics Approval Statement: The Institutional Review Board of the healthcare system reviewed the study protocol, determined it to be exempt and waived informed consent based on the use of existing, HIPAA-deidentified data.