Background Pancreatic cancer is the fourth leading cause of cancer death for men and the fifth for women. The standard treatment for resectable tumours is either a classic Whipple operation or a pylorus- preserving pancreaticoduodenectomy but it is still unclear which of the two procedures is more favourable in terms of survival, mortality, complications, perioperative factors and quality of life. Objectives Several publications pointed out both advantages and disadvantages of both techniques and the current basis of evidence remains unclear. The objective of this systematic review is to compare the effectiveness of each technique. Search strategy A search was conducted to identify all published and unpublished randomised controlled trials. Trials were identified by searching the following electronic databases - The Cochrane Library, MEDLINE, EMBASE and Current Contents. Reference lists from trials selected by electronic searching were hand- searched to identify further relevant trials. Selection criteria Randomised controlled trials ( RCTs) comparing the classical Whipple (CW) with the pylorus- preserving pancreaticoduodenectomy (PPW) were considered eligible if patients with periampullary or pancreatic carcinoma were included. Data collection and analysis Two authors independently extracted data for included studies. A random- effects model was used for pooling data from the different trials. Binary outcomes were compared using odds ratios, continuous outcomes were pooled using weighted mean differences and hazard ratios were used to for the meta- analysis of survival data. The methodological quality of included studies was evaluated independently by two authors according to quality standards and by using a questionnaire that covers different aspects of quality. Main results 1235 abstracts were retrieved and checked for eligibility and seven RCTs were finally included. The critical appraisal revealed vast heterogeneity with respect to methodological quality and outcome parameters. The comparison of overall in-hospital mortality ( odds ratio 0.49; 95% CI 0.17 to 1.40; P= 0.18), overall survival ( hazard ratio 0.84; 95% CI 0.61 to 1.16; P= 0.29) and morbidity showed no significant difference. However, operating time ( weighted mean difference - 68.26 min; 95% CI - 105.70 to - 30.83; P= 0.0004) and intra- operative blood loss ( weighted mean difference - 0.76 ml; 95% CI - 0.96 to - 0.56; P < 0.00001) were significantly reduced in the PPW group. Authors' conclusions There is no evidence of relevant differences in mortality, morbidity and survival between the PPW and the CW. Given obvious clinical and methodological inter-study heterogeneity, future efforts have to be undertaken to perform high quality RCTs of complex surgical interventions on the basis of well defined outcome parameters.