Background: Worldwide, India is the second largest producer of textile goods. However, there are few epidemiological studies from India that have assessed the risk factors associated with byssinosis. Therefore, a case__ampersandsignndash;control study was carried out to find out the risk factors associated with the occurrence of byssinosis. Method: The study was carried out in two textile mills and three Ginning mills located in and around Ahmedabad city during August-2011 to August-2012. Questionnaire for the assessment of respiratory morbidities based on Medical Research Council Questionnaire and American Thoracic Society Questionnaire modified for Indian settings was used. Results: There were 50 cases and 50 controls. Risk factors for byssinosis like smoking cigarettes and working in dusty environment of Opening sections were significantly associated (p__ampersandsignlt;0.001) with the occurrence of byssinosis whereas Body mass Index (BMI) and duration of service were insignificantly associated. A logistic regression analysis showed that smoking and working in dusty worksites of opening sections were independent risk factors for byssinosis. Conclusions: Since heavy smoking is a risk factor for byssinosis, measures should be taken to reduce smoking among textile workers. Traditional machinery should be replaced by enclosed machinery to reduce the risk of byssinosis.