Introduction: Nephrolithiasis has been rising in prevalence worldwide, imposing a significant cost burden on both patients and society in general. Desmodium styracifolium extract (DSE) and RowatinexÂ® are the two stone-eroding pharmaceuticals most commonly used to treat nephrolithiasis in Vietnam. This study aimed to compare the treatment costs and durations between RowatinexÂ® and DSE in Vietnamese patients with nephrolithiasis. Materials and Methods: This was a retrospective cost-of-illness analysis of the information extracted from a public hospitalâ€™s electronic database. This study was based on the prevalence approach, and it focused on the health-care provider perspective. All ambulatory patients who were diagnosed with nephrolithiasis from January 2015 to December 2017 were filtered using specific inclusion and exclusion criteria. Results and Discussion: A total of 1,001 patients who were prescribed RowatinexÂ® and 882 patients who were prescribed DSE were included in this research. The majority were 30â€“59 years old and had no health insurance. The pharmaceutical expenses accounted for the highest percentage of the total cost (59.8% for RowatinexÂ® and 67.9% for DSE). Overall, the RowatinexÂ® treatment had a higher average cost per patient than the DSE (290.5 vs. 264.3 US dollars); however, it was used over a shorter duration of time (10.8 weeks vs. 19.6 weeks). Conclusion: Based on the results of this study, RowatinexÂ® is a more ideal choice for patients with kidney stone disease.