As time evolved, traditional Chinese medicine (TCM) became integrated into the global medical system as complementary treatments. Some essential TCM herbs started to play a limited role in clinical practices because of Western medication development. For example, Fuzi (Aconiti Lateralis Radix Praeparata) is a toxic but indispensable TCM herb. Fuzi was mainly used in poor circulation and life-threatening conditions by history records. However, with various Western medication options for treating critical conditions currently, how is Fuzi used clinically and its indications in modern TCM are unclear. This study aimed to evaluate Fuzi and Fuzi-based formulas in modern clinical practices using artificial intelligence and data mining methods. This nationwide descriptive study with market basket analysis used a cohort selected from the Taiwan National Health Insurance database that contained one million national representatives between 2003 and 2010 used for our analysis. Descriptive statistics were performed to demonstrate the modern clinical indications of Fuzi. Market basket analysis was calculated by the Apriori algorithm to discover the association rules between Fuzi and other TCM herbs. A total of 104,281 patients using 405,837 prescriptions of Fuzi and Fuzi-based formulas were identified. TCM doctors were found to use Fuzi in pulmonary (21.5%), gastrointestinal (17.3%), and rheumatologic (11.0%) diseases, but not commonly in cardiovascular diseases (7.4%). Long-term users of Fuzi and Fuzi-based formulas often had the following comorbidities diagnosed by Western doctors: osteoarthritis (31.0%), peptic ulcers (29.5%), hypertension (19.9%), and COPD (19.7%). Patients also used concurrent medications such as H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, β-blockers, calcium channel blockers, and aspirin. Through market basket analysis, for the first time, we noticed many practical Fuzi-related herbal pairs such as Fuzi-Hsihsin (Asari Radix et Rhizoma)-Dahuang (Rhei Radix et Rhizoma) for neurologic diseases and headache. For the first time, big data analysis was applied to uncover the modern clinical indications of Fuzi in addition to traditional use. We provided necessary evidence on the scientific use of Fuzi in current TCM practices, and the Fuzi-related herbal pairs discovered in this study are helpful to the development of new botanical drugs.