Background: A variety of autoreactive antibodies are detected in patients with chronic liver disease. This prospective, nonrandomized study was undertaken to evaluate the nature & prevalence of various autoantibodies in patients with chronic liver disease of diverse etiologies. Methods: Study population included 53 patients (75% males), who met defined criteria for chronic liver disease. Detailed clinical, laboratory and sonographic evaluation was done. Sera were tested for ASMA, anti-LKM type1, AMA, APA, ANA, by standard methods. P<0.05 was considered significant. Results: Among various etiologies for chronic liver disease, Hepatitis B was most common (28%), followed by alcohol (19%), autoimmune hepatitis in 15%, Hepatitis C (6%) and miscellaneous (2%). 30% of patients were labeled as cryptogenic after detailed investigations. ANA (>1/80) was positive in 100% of definite AIH, 33% of HCV related CLD but at titer of >1/40, 66.6% of HCV related CLD & 60% of probable AIH were found positive. ASMA (>1/40) was positive in 6% of HBV related CLD, 10% of alcohol related CLD, 33% of definite AIH, 40% of probable AIH, 33% of HCV related CLD but ASMA in titer of >1/80 was positive only in 33% oh definite AIH. APA was detected in 12.5% of cryptogenic CLD, 13.3% of HBV related CLD & 20% of alcohol & probable AIH related CLD each. AMA was detected in 1% of cryptogenic, HBV, AIH (definite) & HCV related CLD each, and 2% of alcohol related CLD & 100% of PBC. Conclusions: Apart from AIH there is high prevalence of ANA & SMA in HCV related CLD while other antibodies has low prevalence in non-AIH related CLDs. This study also suggests that prevalence of various autoantibodies should be borne in mind while considering the diagnosis of CLD especially of mixed etiology.