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Background We implemented a preprocedural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening initiative designed to sustain health care during a time when the extent of SARS-CoV-2 infection was unknown. Methods This was a prospective study of patients undergoing procedures at 3 academic hospitals in Pittsburgh, Pennsylvania (April 21–June 11), and 19 community hospitals across Middle/Western Pennsylvania and Southwestern New York (May 1–June 11). Patients at academic hospitals underwent symptom screening ≤7 days preprocedure, then SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) testing 1–4 days preprocedure. A subset also underwent day-of-procedure testing. Community hospital patients underwent testing per local protocols. We report SARS-CoV-2 PCR positivity rates, impact, and barriers to testing encountered through June 11. PCR positivity rates of optional preprocedural SARS-CoV-2 testing for 2 consecutive periods following the screening initiative are also reported. Results Of 5881 eligible academic hospital patients, 2415 (41.1%) were tested (April 21–June 11). Lack of interest, distance, self-isolation, and nursing home/incarceration status were barriers. There were 11 PCR-positive patients (10 asymptomatic) among 10 539 patients tested (0.10%; 95% CI, 0.05%–0.19%): 3/2415 (0.12%; 95% CI, 0.02%–0.36%) and 8/8124 (0.10%; 95% CI, 0.04%–0.19%) at academic and community hospitals, respectively. Procedures were performed as scheduled in 40% (4/10) of asymptomatic PCR-positive patients. Positivity increased during subsequent coronavirus disease 2019 (COVID-19) surges: 54/34 948 (0.15%; 95% CI, 0.12%–0.20%) and 101/24 741 (0.41%; 95% CI, 0.33%–0.50%) PCR-positive patients from June 12–September 10 and September 11–December 15, respectively (P  < .0001). Conclusions Implementing preprocedural PCR testing was complex and revealed low infection rates (0.24% overall), which increased during COVID-19 surges. Additional studies are needed to define the COVID-19 prevalence threshold at which universal preprocedural screening is warranted. [ABSTRACT FROM AUTHOR]