Key Points Question What is the frequency with which patients hospitalized with COVID-19 are treated with venous thromboembolism (VTE) prophylactic- and treatment-dose anticoagulation, and what is the association of anticoagulation with in-hospital and 60-day mortality? Findings In this cohort study of 1351 patients hospitalized with COVID-19 in which 1127 patients received anticoagulation, 34.8% missed 2 or more days of VTE prophylaxis. Use of only prophylactic-dose or treatment-dose anticoagulation was associated with lower in-hospital mortality vs no anticoagulation; however, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. Meaning These findings suggest that prophylactic-dose VTE anticoagulation may be optimal therapy for patients hospitalized with COVID-19., This cohort study of patients hospitalized with COVID-19 examines the association of anticoagulation treatment with mortality rates, and assesses differences between prophylactic- and treatment-doses in in-hospital and 60-day mortality., Importance Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality. Objective To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality. Design, Setting, and Participants This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021. Exposures Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization. Main Outcomes and Measures The effect of nonadherence and anticoagulation strategies on in-hospital and 60-day mortality was assessed using multinomial logit models with inverse probability of treatment weighting. Results Of a total 1351 patients with COVID-19 included (median [IQR] age, 64 [52-75] years; 47.7% women, 48.9% Black patients), only 18 (1.3%) had a confirmed VTE, and 219 (16.2%) received treatment-dose anticoagulation. Use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased over time (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.61 per week). Of 1127 patients who ever received anticoagulation, 392 (34.8%) missed 2 or more days of prophylaxis. Missed prophylaxis varied from 11% to 61% across hospitals and decreased markedly over time (aOR, 0.89; 95% CI, 0.82-0.97 per week). VTE nonadherence was associated with higher 60-day (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.03-1.67) but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03). Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35). Conclusions and Relevance This large, multicenter cohort of patients hospitalized with COVID-19, found evidence of rapid dissemination and implementation of anticoagulation strategies, including use of treatment-dose anticoagulation. As only prophylactic-dose anticoagulation was associated with lower 60-day mortality, prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.