Introduction: Cryptococcosis is a clinically significant systemic mycosis caused by encapsulated yeast of the genus Cryptococcus, predominantly Cryptococcus neoformans and other species of Cryptococcus. These fungi are ubiquitously present in the environment and are acquired primarily through inhalation of infectious propagules, initially affecting the lungs with a strong propensity for hematogenous dissemination to the central nervous system. Cryptococcal meningitis remains one of the leading causes of fungal-related morbidity and mortality, particularly among immunocompromised individuals such as patients with HIV/AIDS, malignancies, organ transplants, or those receiving long-term immunosuppressive therapy. In recent decades, the global burden of cryptococcosis has increased due to the expanding population of immunocompromised hosts, highlighting its importance as an opportunistic pathogen. Early diagnosis and appropriate management are critical for improving patient outcomes. 1,3 Objectives: To determine the prevalence of cryptococcal infection and associated risk factors in patients attending a tertiary care hospital in Eastern Uttar Pradesh. Materials and Methods: A prospective cross-sectional study was conducted in the Department of Microbiology, Moti Lal Nehru Medical College Prayagraj from January to December 2024. A total of 500 clinical specimens including CSF, blood, and BAL fluid were collected from suspected cases of cryptococcal infection. Samples were processed using India ink preparation, culture on Sabouraud Dextrose Agar, KOH preparation, gram stain and urease test. Relevant clinical data, including HIV status and comorbidities, were recorded. Result: Out of 500 samples, 37 (7.6%) were positive for Cryptococcus species. Majority were from CSF (71%). Cryptococcus neoformans was the predominant species (86.8%), followed by other species of Cryptococcus (13.2%). The mean age of affected patients was 36 years, with male predominance (M: F = 2.3:1). HIV infection was the most common underlying risk factor (65.7%), followed by uncontrolled diabetes mellitus (15.7%). Clinically, headache, fever, and altered sensorium were predominant features. Conclusion: Cryptococcus remains an important cause of meningitis in immunocompromised patients in Eastern Uttar Pradesh. Early diagnosis using culture is essential for better outcomes. Strengthen routine screening for cryptococcal infection in high-risk patients is recommended.