There is growing evidence that tobacco smoking is an important risk factor for tuberculosis (TB). India, with a population of 1.26 billion, has the highest number of both TB patients and smokers. The convergence of these two important health hazards is likely severely affecting India's TB control programs. This study was carried out to determine the prevalence of smoking in newly diagnosed pulmonary TB patients and the impact of smoking on disease outcomes in a tertiary care hospital. All patients newly diagnosed with pulmonary TB as per the Revised National Tuberculosis Program of India (RNTCP) 2013 criteria were enrolled in the study. On the basis of their self-reported smoking status, the participants were classified as never smokers, current smokers, and ex-smokers. Patients were started on anti-TB treatment and were followed for 2 years. Among the 2350 subjects (1,758 males and 592 females), 1,593 patients (67.78%) were never smokers. Current and ex-smokers numbered 757 (32.21%), of which 751 (31.95%) were males and 6 (0.26%) were females. Smoking was associated with more extensive lung disease, lung cavitation, and positive sputum smear and culture results at baseline. In both current smokers and ex-smokers, sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment. Ex-smokers and current smokers had significantly high rates of defaults, treatment failures, and relapses. The prevalence of smoking is very high in TB patients. Tobacco smoking is associated with a considerably increased risk of advanced and more severe disease in the form of lung cavitations, positive sputum smear and culture results, and slower smear and culture conversion after initiation of treatment. Smoking has a great negative effect on treatment completion, cure rates, and relapse rates in patients with pulmonary TB.