Background: COVID-19 is associated with variable symptoms and clinical sequelae. Patients who develop respiratory failure and progress to ARDS often have worse outcomes. Studies have examined the clinical course of these patients, finding a prolonged need for invasive ventilation and variable reintubation rates. However, no research has investigated factors and outcomes related to reintubation secondary to respiratory failure among COVID-19 patients with ARDS. Methods: We conducted a single-center, retrospective study on subjects intubated for ARDS secondary to COVID-19. Included subjects had ARDS upon intubation, ventilated for ≥ 24 h, passed a spontaneous breathing trial (SBT), and were electively extubated. The primary outcome was reintubation status; secondary outcomes were hospital and ICU length of stay and mortality. Using a standardized format, we collected various data from the EMR. Data analyzed using SAS, with between-group comparisons using chi-square testing for categorical information and Student t-test for quantitative data. Univariate and multivariate logistic regression was performed to determine factors related to reintubation and mortality as dependent variables. Results: One hundred fourteen subjects were included, of which(32%) required reintubation.No between-group differences detected for most demographic variables or comorbidities. No differences detected in COVID-19 treatments, noninvasive respiratory support, mechanical circulatory support, or duration of ventilation. Midazolam ;P=.002), fentanyl ;P=.02), and APACHE-II scores(OR 1.08[95% CI 1.03-1.147;P=.005) were independently associated with reintubation(AUC=.81). Reintubated subjects had extended hospital(36.7±22.7d vs.26.1±12.1d;P=.01) and ICU(29.6±22.4d vs. 15.8±10.4d;P<.001) stay. More subjects died who failed extubation(49% vs.3%;P<.001). Age (OR 1.07[95%CI: 1.02-1.23];P=.005), male sex(OR 4.9[95% CI 1. 08-22.35];P=.04), positive CAM-ICU ];P =.007), and reintubation ;P<.001)were independently associated with death(AUC=.93). Conclusions: Midazolam, fentanyl, and higher APACHE-II scores were independently associated with reintubation secondary to respiratory failure in subjects with COVID-19-related ARDS. Furthermore, age, male sex, positive CAM-ICU, and reintubation were independently associated with mortality. Reintubation also correlated with prolonged hospital and ICU stay.