Background Medically serious suicide attempts (MSSA) represent a subgroup of clinically heterogeneous suicidal behaviours very close to deaths by suicide. A simple definition of an MSSA is a suicide attempt with life-threatening consequences, regardless of the severity of the attempter’s mental disorder. Few studies have specifically analysed the heterogeneity of MSSA. Therefore, the aim of this study is to describe the profile of individuals who made a highly severe MSSA and to compare those admitted to Intensive Care Units (ICU) – including Burn Units– with other MSSA admitted to other medical and surgical units. Methods The study sample consisted of 168 patients consecutively admitted to non-psychiatric wards from two public hospitals in Barcelona after an MSSA during a 3-year period. In order to select more severe MSSA, the minimum hospital stay was expanded from Beautrais’ definition of ≥ 24 h to ≥ 48 h. Mean hospital stay was 23.68 (SD = 41.14) days. Patients needing ICU treatment (n = 99) were compared to other MSSArs (n = 69) that were admitted to other medical and surgical units, not requiring intensive care treatment, with an initial bivariant analysis followed by a logistic regression analysis using conditional entrance. Results Medically serious suicide attempters (MSSArs) spent more time hospitalized, more frequently reported recent stressful life events, were more likely to have at least one prior suicide attempt (SA) and their current attempt was more frequently non-planned, compared to the profile of MSSArs reported in previous studies. The most frequent method was medication overdose (67.3%) and jumping from heights (23.2%). Among those who chose more than one method (37.6%), the most frequent combination was medication overdose and drug use. Affective disorders and personality disorders were the most frequent diagnoses. Higher educational level, history of previous mental disorders and prior lifetime suicide attempts were significantly more frequent among those admitted to ICU compared to other MSSArs. Patients needing admission to ICU less frequently used self-poisoning and cuts. Conclusions MSSA needing ICU admission can be regarded clinically as similar to attempts resulting in suicide. More research on this type of highly severe suicide behaviour is needed due to its serious implications both from a clinical and public health perspective.