Background: Rituximab, one of the most commonly used biologics, was once approved by the United States Food and Drug Association (US FDA) for the management of different systemic autoimmune disorders, and it is now used extensively in managing off-label indications. There is a scarcity of data regarding its utilization pattern in India. Objective: To assess rituximab usage pattern in two tertiary care hospitals of Central India. Methods: A cross-sectional, retrospective study was performed to analyze the data of patients from two tertiary care centers of Central India who had received rituximab between 2019 and 2021. The usage was categorized either for FDA-approved indications or for off-label indications. Multiple logistic regression was applied to evaluate which factors would influence the use of rituximab for an FDA-approved indication. Results: A total of 79 medical records of patients. The majority of the patients (77.2%) had received rituximab for an FDA-approved indication. The most common approved and off-label indications detected were non-Hodgkin's lymphoma and autoimmune disorders, respectively. The use of rituximab for an FDA-approved indication was associated with increased age (adjusted odds ratio [AOR] = 1.04, 95% confidence interval [CI] = 0.99–1.1), male sex: AOR = 2.55, 95% CI = 0.74–9.93, malignancy: AOR = 9.39, 95% CI = 1.46–76.12, and diabetes: AOR = 1.38, 95% CI = 0.19–13.74. Conclusions: The use of rituximab was more common for an FDA-approved indication rather than for an off-label indication. Factors such as advancing age, male sex, and malignancy were frequently associated with the FDA-approved use of rituximab.