Introduction: Lower limb cellulitis is a common superficial skin infection that leads to morbidity and mortality. Cellulitis risk factors have been well studied in many countries, but to date, not in Malaysia. Geographical and climate variables may affect risk factors. Early identification of the preventable risk factors is vital to prevent cellulitis and improve holistic patient care. Objective: To determine the risk factors of lower limb cellulitis amongst hospitalized patients at a tertiary center. Methods: A prospective case-control study of hospitalized patients with a clinical diagnosis of lower limb cellulitis was conducted at UKM Medical Centre, January–August 2015. Each patient was compared to two age and gender-matched control patients. All patients were interviewed and examined for risk factors of cellulitis. Results: A total of 96 cellulitis patients and 192 controls participated in this study. The cellulitis patients included 61 males and 35 females with a mean age of 62.07±15.43 years. The majority of patients were experiencing their first episode of cellulitis. Multivariate analysis showed a previous history of cellulitis (OR 25.53; 95% CI 4.73–137.79), sole anomalies (OR 16.32; 95% CI 6.65–40.06), ulceration (OR 14.86; 95% CI 1.00–219.39), venous insufficiency (OR 10.46 95% CI 1.98–55.22), interdigital intertrigo (OR 8.86; 95% CI 3.33-23.56), eczema (OR 5.74; 95% CI 0.96.–34.21), and limb edema (OR 3.95; 95% CI 1.82–8.59) were the significant risk factors for lower limb cellulitis. Conclusion: Previous cellulitis and factors causing skin barrier disruption such as sole anomalies, ulceration, venous insufficiency, eczema, intertrigo, and limb edema were the risk factors for lower limb cellulitis. Physician awareness, early detection, and treatment of these factors at the primary care level may prevent hospital admission and morbidity associated with cellulitis.