The authors present three patients with acalculous cholecystitis seen at a tertiary care center in Bangkok. The first patient was explored surgically because peritonitis was suspected. The two other patients were treated conservatively with antibiotics and supportive care, and they recovered fully. The diagnosis of leptospirosis was confirmed by increasing antibody titers in three patients and by blood culture in one patient. Leptospira were not detected in the surgical specimen. Leptospirosis is a systemic disease that can present with a multitude of symptoms and signs including right upper quadrant pain mimicking cholecystitis. A high level of awareness and appropriate laboratory studies should allow early diagnosis and may prevent unnecessary surgical intervention.