Context: Respiratory diseases are one of the leading causes of deaths world-wide. There are no published studies on the pattern and determinants of respiratory mortality from South India. Aims: The aim was to find out the pattern and determinants of respiratory mortality during July 1, 2002 to June 31, 2008 in Varkala, Thiruvananthapuram district, Kerala. Settings and Design: A nested case control study from a prospective cohort was done to find out the determinants for respiratory mortality. The main outcome measure was mortality due to respiratory causes. Materials and Methods: The data collected here are from the Population Registry of Lifestyle Diseases study, a prospective cohort study involving the long-term followup of the residents of Varkala rural development block Thiruvananthapuram district of South Kerala. Statistical analysis used: The age specific respiratory mortality rate was calculated. Chi-square test and odds ratio (OR) were measured to find out the association between exposure and outcome variables. Logistic regression was performed. Results: A total of 3467 deaths were reported among 77881subjects above the age group of 20 years during the follow-up period. Of which 531 (15.9%) were due to respiratory causes. On logistic regression smoking (AdjOR [95% confidence interval]; 1.65 [1.25, 2.17]), lower socioeconomic status (AdjOR; 1.52 [1.24, 1.87]), lower educational status (AdJOR; 2.22 [1.15, 4.29]) and old age (>60 years) (AdjOR; 2.6 [2.03, 3.33]) were found to be the significant risk factors for respiratory mortality. Conclusion: Mortality due to respiratory causes was found to be high in Kerala, a state which has the best health indicators compared to other states in India.