Background Carpal tunnel decompression surgery (CTD) to treat carpal tunnel syndrome (CTS) is a commonly undertaken procedure, despite a scarcity of data on safety and effectiveness in the general population. We estimated the incidence of reoperation and serious post-operative complications (requiring admission to hospital or further surgery) following CTD in routine clinical practice, and the patient factors associated with adverse outcomes. Methods We included all CTD surgeries undertaken in England using the Hospital Episode Statistics dataset linked to mortality records from 01/04/1998 until 31/03/2017. Patients were followed up until death or 31/03/2017. Primary outcomes were the overall incidence of CTD reoperation and postoperative complications (surgical site infection or dehiscence, neurovascular or tendon injury requiring admission to hospital or further surgery) within 30 and 90 days of surgery. Multivariable Cox regression analysis was used to identify factors influencing complications and reoperation. The Fine and Gray method was used to adjust for the competing risk of mortality. Findings 855 838 CTDs were performed during the 19-year period (incidence rate 1.10 per 1000 person years [95% CI 1·02 to 1·17]). Serious complication rates were 0·07% (95% CI 0·067 to 0·078) within 30 days, 0·08% (95% CI 0·073 to 0·085) within 90 days. 90-day local complications were associated with male sex and age category 18-29 years (adjusted hazard ratios 2·32 [1·74 to 3·09], 2·25 [1·10 to 4·62] respectively). 3·4% underwent CTD reoperation (incidence rate 3·18 per 1000 person years [95% CI 3·12 to 3·23]). Male sex, increasing age, greater levels of comorbidity, and increasing socioeconomic deprivation were associated with increased reoperation risk (adjusted subhazard ratios 1·09 [95% CI 1·05 to 1·13]; 1·09 [1·03 to 1·15]; 1·25 [1·19 to 1·32] and 1·18 [1·10 to 1·27]). Interpretation This is the largest national study on CTD to date, providing the best available evidence on serious post-operative complication and reoperation rates. CTD is a safe operation, with an overall complication rate of less than 0.1%.