Context: About 10,000 babies with β-thalassemia major are born every year in India, posing a major healthcare burden on the country. In clinically symptomatic individuals, monthly blood transfusions, chelation therapy and splenectomy are the mainstay of therapy at present. Aims: To objectively assess the impact of splenectomy on quality of life (QOL) of children with β-thalassemia presenting with symptomatic hypersplenism. Settings and Design: This is a prospective study of thalassemic children referred to pediatric surgical unit of a tertiary care hospital located in Maharashtra, India between January 2010 and December 2012. Materials and Methods: Of 360 cases registered at the thalassemia unit of the center during above defined period, 50 cases (35 males and 15 females) between 5 and 16 years underwent splenectomy. QOL was assessed objectively by means of the composite QOL index calculated by summing-up the responses to a 10-item, 4-point disease specific response scale devised, especially for purpose of the present study; preoperatively and 2 years postoperatively and comparison between the two was carried out. This is the first ever study of this kind. Statistical Analysis Used: Chi-square test was used for statistical analysis in the present study. Results: The mean preoperative QOL index of 13.5 rose to 31.3 (over a scale of 40) 2 years following splenectomy. The “P value” calculated by comparison between the preoperative and postoperative composite QOL index is >0.001 that is, statistically significant. Conclusions: Splenectomy has a definite role in the management of children with β-thalassemia, presenting with hypersplenism. Objective assessment of QOL indicates mean elevation of QOL index by 17.8, thus emphasizing significant impact of splenectomy on the overall QOL of these children.