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Aim Non-vitamin K antagonist oral anticoagulants (NOACs) were developed as an alternative to warfarin to prevent thromboembolism in patients with atrial fibrillation (AF), prosthetic heart valves, venous thromboembolism (VTE), or other thrombotic disorders. The aim of this study is to explore the trends in prescribing OACs, including warfarin and NOACs, in Shanghai, China. Methods Prescription data of OACs were retrospectively collected from Rx Analysis System from 2010 to 2020 in Shanghai, China. Comparisons were made on the trends of each OACs according to different indications, age groups, and hospital grades. The costs and the contribution of individual OACs were also explored. Results Growing trends in overall prescriptions for OACs were observed. The prescriptions of NOACs were significantly increased since 2016, while the prescriptions of warfarin kept decreasing since 2017. A highly statistically significant increase in prescriptions of Rivaroxaban was observed from 2016 to 2020 ( P < .001). Despite the price reduction of rivaroxaban in 2018, the total cost of rivaroxaban continued to rise ( P < .001). Rivaroxaban emerged as a preferred NOAC in both indications of AF and VTE, and accounted for more than three-quarters of the total costs for OACs since 2019. Compared with rivaroxaban, the prescription numbers of dabigatran and apixaban were much smaller, and the growth of prescriptions were much slower. Differences in prescribing patterns in different indications, age groups, and grades of hospitals were also founded. Conclusion There has been a rapid increase in the use of OAC over the last 11 years in Shanghai, China. NOACs have been adopted rapidly, and have been gradually replacing warfarin. Warfarin remains the top choice for certain patients with valvular heart disease. Future studies are warranted considering changes in the OAC use in a larger scale, as well as the rationality and its influence factors on OAC use.