This study aimed to assess different screening strategies in order to allow safe reopening of universities in the United States. An epidemic model was used that captured the epidemiology of SARS-CoV-2, the natural history of COVID-19 illness, and regular mass screening to detect and contain the virus in a college setting. The hypothetical cohort included 5,000 students, with 4,990 students without SARS-CoV-2 and 10 with undetected, asymptomatic SARS-CoV2 at the start of the semester. With screening every 1, 2, 3, or 7 days with a 70% sensitivity and 98% specificity, the result was 162, 243, 379, and 1840 infections, respectively. In the cost-effectiveness analysis, it was found that the screening costs using a test with 70% sensitivity would amount to $470, $910, $120 per student per 80-day period in the base-case (screening every 2 days), worst-case (daily screening), and best-case scenario (weekly screening). It is important to note that the specificity of the test is much more important than the sensitivity. Overall, this study suggests that a fast, inexpensive and poorly sensitive test (>70%) with an Rt of < 2.5 combined with strict adherence to prevention measures is cost-effective and can control the number of COVID-19 infections to allow students to safely return to campus. However, some challenges include the number of false-positives that may overburden housing capacity for isolation.