Gall bladder cancer (GBC) is a leading cause of cancer-related mortality in the northern parts of the Indian subcontinent. A majority of patients with GBC are middle-aged women, who normally would have substantial family responsibilities. Most patients are diagnosed with advanced cancer and are suitable for palliative care only. There is a strong association between long-standing gallstone disease and the development of GBC. Although randomized trials are lacking, prospective population-based data from low-risk and high-risk regions reveal that cholecystectomy reduces the mortality from GBC. Prophylactic cholecystectomy is recommended in populations with high incidence of GBC. The morbidity and mortality of laparoscopic cholecystectomy in uncomplicated gallstone disease is very low in India. Because of these reasons we argue that prophylactic cholecystectomy should be offered to young healthy women from high-risk regions of India whenever they are diagnosed to have asymptomatic gallstones. Simultaneously, population-based observational studies could be undertaken to generate more evidence.