BACKGROUND: Atraumatic splenic ruptures (ASR) are rare but potentially life-threatening events. Little is known about the etiology and the risk factors influencing mortality. AIM: Characterization of predisposing etiological factors and identification of predictive factors for ASR-related mortality. METHODS: Systematic literature review from January 1980 to June 2008 limited to patients aged >18 years. Statistics: logistic regression analysis. RESULTS: Identification of 633 publications reporting on 845 patients. There was a 2:1 male predominance. Mean age was 44.9±16.7 years (median 45, range: 18-86 years). In 59 patients (7%) the spleen was normal and no predisposing factor was identified (atraumatic-idiopathic splenic rupture). One, 2 or 3 predisposing factors were found in 711 (84.1%), 69 (8.2%) and 6 patients (0.7%), respectively (atraumatic-pathologic splenic rupture). Six major etiological groups were defined: a) neoplastic disorders (malignant 16.4% and non-malignant hematological disorders 2%, primary neoplastic 8.1% and secondary metastatic disorders of the spleen 3.8%), b) infectious disorders (viral 14.9%, bacterial 6.5%, protozoal 5.8%, fungal 0.1%), c) inflammatory, non-infectious disorders (pancreatitis 11%, amyloidosis 3.8%, vascular 2.2%, genetic 1.7%, autoimmune 1.4%), d) drug-induced disorders (9.1%), e) mechanic disorders (pregnancy-related 4.3%, congestive splenomegaly 2.5%) and f) normal spleen (6.4%). Splenic rupture was diagnosed by laparotomy 42.3%, computed tomography 32.4%, ultrasound 18.6%, scintigraphy 0.7%, laparoscopy 0.5%, angiography 0.3% or at autopsy 5.2%. Therapy consisted of total splenectomy 84.4%, splenorrhaphy 0.9% or conservative measures 14.7%. Splenomegaly was found in 55%. ASR-related mortality was 12.2%. Multivariate analysis found splenomegaly (odds ratio [OR] 2.337, standard error [SE] 0.967, 95% confidence interval [CI] 1.038-5.258, P=0.04) and age >40 years (OR 1.939, SE 0.472, CI 1.203-3.126, P=0.007) to be associated with mortality. Male gender, primary operative treatment and the coincidence of multiple predisposing factors were not related with mortality. Neoplastic disorders were associated with an increased ASR-related mortality (OR 2.634, SE 0.541, CI 1.762-3.938, P=0.008) compared to the other etiological groups. Patients with an atraumatic-idiopathic splenic rupture (normal spleen, group f) showed a decreased ASR-related mortality (OR 0.111, SE 0.112, CI 0.015-0.807, P=0.03). CONCLUSIONS: Most ASR are atraumatic-pathologic splenic ruptures. Splenomegaly and advanced age are negative predictive factors for survival. Neoplastic disorders are associated with an increased rupture-related mortality.