Setting : Department of Respiratory Medicine, B.Y.L. Nair Hospital, Mumbai, India. Objective : To study pre-treatment sputum smear, culture and drug susceptibility testing for mycobacterium tuberculosis in fresh cases of pulmonary tuberculosis, the extent of laboratory related problems and correlation of the laboratory results with clinical outcome. Design : This study is a prospective analysis of 57 cases of pulmonary tuberculosis that denied previous treatment with anti tuberculosis drugs. Cases with associated human immunodeficiency virus (HIV) infection and diabetes mellitus (DM) were excluded. Pre-treatment smear, culture and drug susceptibility were performed by standard culture techniques. Patients were treated with short course chemotherapy (SCC) on the basis of World Health Organisation (WHO) category I. Laboratory results were correlated with initial clinical data and treatment outcomes. Results : Of the 57 cases selected, there were 34 males and 23females, age range 18-65 years, mean age 27.86 years. Clinical data was lacking in 16 patients who defaulted on treatment and hence were excluded from the analysis. Of the 41 cases with complete data, 37 patients were declared cured (91.25%) while 4 patients failed on therapy (9.75%), 17/41 (41.46%) had laboratory results consistent with clinical data and treatment results whereas 24/41 (58.53%) had poor correlation between laboratory results, clinical data and treatment outcomes. The major laboratory related problems were: 1) Smear positive / culture negative (S+/C-) in 16/41 (39%) cases at the start of treatment; 2) HR pattern of resistance in 4/41 (9.75%) and R resistance 3/41 (7.31%) on initial culture susceptibility tests but response to SCC suggesting incorrect susceptibility results. Conclusions : Discrepant reports between clinical findings, laboratory reports and treatment outcomes were found in 58.53% cases. Treatment should not be decided only on the basis of the initial culture susceptibility testing to avoid unnecessary and toxic second line therapy. Improvement in standardisation and new reliable diagnostic techniques are required for management of TB.