Latent tuberculosis infection (LTBI) is characterized by the presence of immune responses to Mycobacterium tuberculosis without clinical evidence of active TB. LTBI treatment among persons at risk for progression to active disease is an important strategy for TB control and elimination. This prospective observational study aimed to compare the incidences of hepatitis and side effects between a new 2‑month combination regimen of isoniazid, rifampin and pyrazinamid (2HRZ) plus excipient and the standard 3‑month regimen of isoniazid and rifapentine (3HP) for LTBI treatment in Taiwan. Materials and Methods: Between January 1, 2017, and December 31, 2017, all patients aged ≥20 years diagnosed LTBI were included in the study. Demographic and baseline laboratory assessment of the patients at diagnosis was collected. Eligible individuals were allocated to the 2‑month regimen comprising HUEXC030, isoniazid, rifampin, and pyrazinamide (2HRZ) or 3‑month regimen with isoniazid and rifapentine (HP). All symptoms and side effects during treatment were recorded. Results: Nineteen patients received the 2‑month regimen with HRZ plus HUEXC030, while 23 received the 3‑month regimen with HP. The treatment completion rates were 73.7% and 82.6% in the 2‑ and 3‑month regimen groups, respectively. The most common side effects during treatment were fatigue/myalgia/weakness, loss of appetite, and rash. The aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels were similar in both groups after 4 weeks of treatment. Conclusions: This study demonstrates that LTBI patients receiving the 2‑month regimen with HRZ plus HUEXC030 experienced similar side effects including hepatitis as patients on the 3‑month regimen with HP. This new combination treatment regimen may be an alternative for the treatment of LTBI.