Abomasal ulcers are difficult to diagnose clinically with limited therapeutic approach to combat the disease. Omental bursitis (OB) and local peritonitis (LP) are known sequelae of abomasal ulcer in cows. In this study, differentiation between OB and LP in regard to clinical symptoms, biochemical analyses and the response to treatment in Buffaloes was done. Twenty buffaloes (Bubalus bubalis) were admitted with a history of intermittent appetite, wasting and mild abdominal distension during the period between March 2016 and August 2018. All cases were female (12 recently calved, 2 pregnant, 6 non-pregnant) aging from 3 to 9 years and weighing 350–600 kg. For comparison, 10 apparently healthy non-pregnant female buffaloes were used as controls. Abdominal ultrasonography confirmed the presence of 11 OB and 9 LP in admitted cases. Laboratory analysis revealed hyperproteinemia and hypoalbuminemia in OB. Hypokalemia and hypochloremia were detected in both OB and LP. Ultrasonography showed hypo-anechoic content with echoic stippling surrounded by echogenic wall in OB, whereas echogenic strands interspersed with anechoic fluid was reported in LP. Intra-lesional lavage by normal saline was applied several times under ultrasongraphic guidance followed by gentamicin 10% intramuscular and H2 antagonist intravenous for 5 days as well as parenteral and enteral fluid therapy. Seven cases of OB clinically improved, whereas no improvements were found in LP cases. OB secondary to abomasal ulcer has a good prognosis in contrast to LP. Ultrasonography provides a useful diagnostic tool and therapeutic guidance for such diseases.