Background and Objective: India, a highly heterogeneous country, has no common reference standards for predicting spirometry values, with very few recent studies from south India. This study aimed to create reference equations for rural south Indian adults, based on a population-based survey in Vellore, south India and compare it with other equations from India. Methods: The data from 583 non-smoking, asymptomatic participants (30 years and older) from a spirometry-based survey for airflow obstruction (rural Vellore, 2018), were used to develop equations for FEV1, FEV1/FVC, and FVC. The dataset was divided for development (70%) and validation (30%), by gender. Differences between observed and predicted values were assessed using the new equations and comparisons made with other equations from India. Results: Predictions with Vellore rural equations were closest to the previous south Indian equations from urban Bangalore. However, the Bangalore equations led to overestimation of FVC values in males, and of both FEV1 and FVC values in females. Using the rural Vellore equations also led to a higher percent of males being classified as having airflow obstruction, compared to the Bangalore equations which underestimated airflow obstruction in this rural population. Comparison with previously derived Indian equations from other parts of the country showed pronounced variations. Conclusions: Our study reiterates the need for representative rural and urban studies of adults from various parts of India, to obtain region specific reference equations, given the wide variations in spirometry values in “normal” individuals, due to social heterogeneities of the Indian population and resulting complexities in defining normal.