The aim of this study was to evaluate the impact of acute cholecystitis (AC), obesity, and previous abdominal surgery on laparoscopic cholecystectomy (LC) outcomes. Records of 1940 patients undergoing LC in 1992 and 2004 were reviewed in order to assess the independent and joint effects of the above risk factors on conversion, morbidity, operation time, and hospital stay. In multivariate regression analysis, adjusting for sex and age, AC alone and in combination with obesity or previous abdominal surgery increased the risk of conversion and complications and was associated with prolonged operation time and hospital stay compared with the patients without any of the risk factors (reference group). The independent and joint effects of obesity and previous abdominal surgery were significant only on operation time. On the contrary, previous upper abdominal surgery alone and in combination with AC was associated with 3- and 17-fold relative odds of conversion, respectively. The combined presence of AC, obesity, and previous abdominal surgery yielded an odds ratio for conversion of 7.5 and for complications of 10.7, as well as a longer operation time and hospital stay. The presence of previous upper abdominal surgery with AC and obesity had a substantial effect on conversion, with an odds ratio of 87.1 compared with the reference group. LC is safe in patients with AC, previous abdominal surgery, or obesity. However, the presence of inflammation alone or in combination with obesity and/or previous (especially upper) abdominal surgery is the main factor that influences the adverse outcomes of LC.