Purpose: To assess the impact of variables related to setting, study design and definition on adverse outcome occurrence and mortality in hospitalized patients. Data sources: Pubmed and Embase. Study selection: Articles in English from 1980 onwards, in non-selected patients or surgical patients only. Data extraction: Data were extracted independently by two authors using a predefined form. Included study methodology variables were general variables such as setting, patient variables like age, study variables like number of reviewers and definition and the resulting adverse outcome occurrence and mortality. Results: Eleven studies reporting on 76 617 non-selected patients and 18 studies representing 136 292 surgical patients were included. Adverse outcomes were estimated to occur in 16% (12-19%) of non-selected patients and in 18% (14-22%) of surgical patients, taking into account the heterogeneity between studies. The study methodology variables were not statistically significant in explaining variation in adverse outcome occurrence, but the individual studies, when used as a random effect variable, were significant. Conversely, the study variable was not significant to explain variation in mortality rates, whereas the study methodology variables were: having more than one reviewer increased mortality by 30-80%, older study populations resulted in higher mortality and including a cause in the definition halved the mortality rate. Conclusion: Study methodology variables do not explain differences in adverse outcome occurrence between studies. Other inter-study differences are more important. However, study methodology is an important predictor for mortality differences and should be taken into account when interpreting differences between studies.@en