Cholelithiasis, or gallstone disease, is a prevalent gastrointestinal disorder caused by complex interactions of genetic, metabolic, and lifestyle factors. This study aimed to determine the prevalence, clinical presentations, and preventive practices associated with cholelithiasis in patients undergoing cholecystectomy at a tertiary care hospital. Methods: A prospective observational study was conducted over six months (September 2023–February 2024) at Narayana Medical College and Hospital, Nellore, involving 150 patients diagnosed with cholelithiasis. Data were collected through patient interviews and a structured proforma documenting demographics, clinical history, risk factors, investigations, and treatment outcomes. Statistical analyses were performed to identify patterns and associations. Results: The majority of participants were in the 51– 60 age group (31%), with females (56.5%) slightly outnumbering males (43.5%). Most patients (60%) had a "Good" nutritional status, while 25% were categorized as "Poor." The predominant symptom was upper abdominal pain (75%), and ultrasonography was the most frequently used diagnostic tool (80%). Mixed pigment stones were the most common type (64%), followed by cholesterol stones (13.5%). Key complications included choledocholithiasis (40%) and fatty liver (21%). Hypertension (21.5%) and diabetes mellitus (20.5%) were the most common comorbidities. Lifestyle factors such as alcohol consumption (25%) and smoking (20%) were identified as risk factors. Post-treatment outcomes were highly favorable, with 92.5% of patients achieving complete recovery. Conclusion: This study highlights the multifactorial nature of cholelithiasis, with age, gender, nutritional status, and lifestyle factors playing significant roles in its prevalence. Ultrasonography remains the cornerstone for diagnosis, and laparoscopic cholecystectomy is an effective treatment. These findings underscore the importance of early detection and lifestyle modifications as preventive measures to reduce the burden of gallstone disease