Abstract: We identified seven trials that met the inclusion criteria. Out of these, six trials provided data for the meta-analyses. A total of 488 participants with acute cholecystitis and fit to undergo laparoscopic cholecystectomy were randomised to early laparoscopic cholecystectomy (ELC) (244 people) and delayed laparoscopic cholecystectomy (DLC) (244 people) in the six trials. Blinding was not performed in any of the trials and so all the trials were at high risk of bias. Other than blinding, three of the six trials were at low risk of bias in the other domains such as sequence generation, allocation concealment, incomplete outcome data, and selective outcome reporting. The proportion of females ranged between 43.3% and 80% in the trials that provided this information. The average age of participants ranged between 40 years and 60 years. There was no mortality in any of the participants in five trials that reported mortality. There was no significant difference in the proportion of people who developed bile duct injury in the two groups (ELC 1/219 (adjusted proportion 0.4%) versus DLC 2/219 (0.9%); Peto OR 0.49; 95% CI 0.05 to 4.72 (5 trials)). There was no significant difference between the two groups (ELC 14/219 (adjusted proportion 6.5%) versus DLC 11/219 (5.0%); RR 1.29; 95% CI 0.61 to 2.72 (5 trials)) in terms of other serious complications. None of the trials reported quality of life from the time of randomisation. There was no significant difference between the two groups in the proportion of people who required conversion to open cholecystectomy (ELC 49/244 (adjusted proportion 19.7%) versus DLC 54/244 (22.1%); RR 0.89; 95% CI 0.63 to 1.25 (6 trials)). The total hospital stay was shorter in the early group than the delayed group by four days (MD -4.12 days; 95% CI -5.22 to -3.03 (4 trials; 373 people)). There was no significant difference in the operating time between the two groups (MD -1.22 minutes; 95% CI -3.07 to 0.64 (6 trials; 488 people)). Only one trial reported return to work. The people belonging to the ELC group returned to work earlier than the DLC group (MD -11.00 days; 95% CI -19.61 to -2.39 (1 trial; 36 people)). Four trials did not report any gallstone-related morbidity during the waiting period. One trial reported five gallstone-related morbidities (cholangitis: two; biliary colic not requiring urgent operation: one; acute cholecystitis not requiring urgent operation: two). There were no reports of pancreatitis during the waiting time. Gallstone-related morbidity was not reported in the remaining trials. Forty (18.3%) of the people belonging to the delayed group had either non-resolution of symptoms or recurrence of symptoms before their planned operation and had to undergo emergency laparoscopic cholecystectomy in five trials. The proportion with conversion to open cholecystectomy was 45% (18/40) in this group of people. We found no significant difference between early and late laparoscopic cholecystectomy on our primary outcomes. However, trials with high risk of bias indicate that early laparoscopic cholecystectomy during acute cholecystitis seems safe and may shorten the total hospital stay. The majority of the important outcomes occurred rarely, and hence the confidence intervals are wide. It is unlikely that future randomised clinical trials will be powered to measure differences in bile duct injury and other serious complications since this might involve performing a trial of more than 50,000 people, but several smaller randomised trials may answer the questions through meta-analyses.

Plain-language summary: Six trials providing information on the review question were identified. A total of 488 people with acute cholecystitis were included. Laparoscopic cholecystectomy was performed early (within seven days of people presenting to the doctor with symptoms) in 244 people while it was performed after at least six weeks in the remaining 244 people. The proportion of females ranged between 43.3% and 80% in the trials that provided this information. The average age of participants ranged between 40 years and 60 years. All the trials were at high risk of bias (and might have overestimated the benefits or underestimated the harms of either early laparoscopic cholecystectomy or delayed laparoscopic cholecystectomy). All the people included in the trials were discharged home alive after operation in the five trials from which this information was available. There was no significant difference in the proportion of people who developed bile duct injury, surgical complications, or who required conversion from key-hole to open operation between the two groups. None of the trials reported quality of life from the time of randomisation. The total hospital stay was shorter in the early group than the delayed group by four days. There was no significant difference in the operating time between the two groups. Only one trial reported the time taken for employed people to return to work. The people belonging to the early laparoscopic cholecystectomy group returned to work 11 days, on average, earlier than the delayed laparoscopic cholecystectomy group. Four trials did not report any gallstone-related complications during the waiting period. One trial reported five gallstone-related complications, including two people with cholangitis. There were no reports of pancreatitis during the waiting time. Gallstone-related morbidity was not reported in the remaining trial. Approximately one-sixth of people belonging to the delayed group had either non-resolution of symptoms or recurrence of symptoms before their planned operation and had to undergo emergency laparoscopic cholecystectomy in five trials. Based on information from a varied number of participants as well as trials at high risk of bias, early laparoscopic cholecystectomy during acute cholecystitis appears safe and shortens the total hospital stay. The majority of the important outcomes occurred rarely and hence one cannot rule out that future trials may show that one treatment or another may be better in terms of complications. However, the trial size required to show such differences involves a clinical trial on more than 50,000 people and so it is unlikely that such large trials will be performed. Several smaller randomised trials may answer the questions through meta-analyses.