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Mortality of generalized postoperative peritonitis remains high at 22% to 55%. The aim of the present study was to identify prognostic factors by means of univariate and multivariate analysis in a consecutive series of 96 patients. Mortality was 30%. Inability to clear the abdominal infection or to control the septic source, older age, and unconsciousness were significant factors related to mortality in the multivariate analysis. Failure to control the peritoneal infection (15%) was always fatal and correlated with failed septic source control, high Acute Physiology and Chronic Health Evaluation (APACHE) II score, and male gender. Failure to control the septic source (8%) also was always fatal and correlated with high APACHE II score and therapeutic delay. In patients with immediate source control, residual peritonitis occurred in 9% after purulent or biliary peritonitis and in 41% after fecal peritonitis (p = 0.002). In patients without immediate control of the septic source, delayed control was still achieved in 100% after a planned relaparotomy (PR) strategy versus 43% after an on-demand relaparotomy (ODR) strategy (p = 0.018). In the same patients, mortality was 0% in the PR group versus 64% in the ODR group (p = 0.007). Early relaparotomy is related to improved septic source control. After relaparotomy for generalized postoperative peritonitis, a PR strategy is indicated whenever source control is uncertain. It also might decrease mortality in fecal peritonitis. An ODR approach is adequate for purulent and biliary peritonitis with safe septic source control.