The complex regional pain syndrome (CRPS) is a painful disorder that can occur in an extremity after any type of injury, or even spontaneously. Data on the incidence of CRPS are scarce and mostly hospital based. Therefore the size of the problem and its burden on health care and society are unknown. The objective of the present study was to estimate the incidence of CRPS in the general population. A retrospective cohort study was conducted during 1996-2005 in the Integrated Primary Care Information (IPCI) project, a general practice research database with electronic patient record data from 600,000 patients throughout The Netherlands. Potential CRPS cases were identified by a sensitive search algorithm including synonyms and abbreviations for CRPS. Subsequently, cases were validated by electronic record review, supplemented with original specialist letters and information from an enquiry of general practitioners. The estimated overall incidence rate of CRPS was 26.2 per 100,000 person years (95% CI: 23.0-29.7). Females were affected at least three times more often than males (ratio: 3.4). The highest incidence occurred in females in the age category of 61-70 years. The upper extremity was affected more frequently than the lower extremity and a fracture was the most common precipitating event (44%). The observed incidence rate of CRPS is more as four times higher than the incidence rate observed in the only other population-based study, performed in Olmsted County, USA. Postmenopausal woman appeared to be at the highest risk for the development of CRPS.