Objective Adults with refractory epilepsy proposed for elective ablative surgery have a high prevalence of interictal psychopathology, mostly due to mood and anxiety disorders. Most studies show post-surgical remission of depressive and anxiety symptoms in a significant percentage of patients, although de novo psychopathology after surgery has also been described: affective disorders (4%–18.2% of the cases), anxiety disorders (7%–13%) and psychotic symptoms (1%–5%). In the present study we assessed the incidence of the novo psychopathology and the evolution of pre-existing psychopathology in a sample of epilepsy patients submitted to ablative surgery. Method 13 consecutive adult patients with refractory epilepsy, eligible for ablative surgical treatment, were assessed pre-operatively (unstructured psychiatric interview and Mini International Neuropsychiatric Interview) and on repeated occasions post-operatively for a variable period of time. Results We followed up 4 men and 9 women. Mean age at the time of surgery was 40.7±3.7 years. We divided the post-surgical follow-up period in three phases: immediate (first 4 weeks), intermediate (2–12 months) and late (>12 months). Psychopathology was a frequent occurrence in the immediate (53.8% of cases), intermediate (41.7%) and late (85.7%) post-operative period. We found no association between pre-surgical psychopathology and surgery outcome in terms of epilepsy remission. We found an association between female gender and psychopathology in the first year post-surgery (p=0.038; χ2=4.29). No gender effects were found in terms of pre-surgical psychopathology or psychopathology in the immediate or late post-surgical period. Hippocampectomy plus amygdalectomy was associated with a higher incidence of psychopathology in the first month and in the first year after surgery (6/8 vs 1/5, χ2=3.75; p=0053 and 5/7 vs 0/5, χ2=6.12; p=0.013, respectively). None of the four patients submitted to amygdalectomy with hippocampus sparing developed any psychopathology in these two post-surgical periods (χ2=6.74; p=0009 e χ2=4.29; p=0.038, respectively). Left hemisphere interventions were also associated with increased risk of late (i.e., >12 months post-surgery) depression in this sample (2/2 vs. 1/5, χ2=3.73; p=0.053). Preoperative psychopathology was significantly associated with psychopathology in the first 12 months post-surgery (3/3 vs 2/9, p=0.018; χ2=5.6), but not in the immediate or late post-surgical periods. Pre-surgical psychopathology was associated with a higher incidence of major depression in the first year post-surgery, but not in the late post-surgical period. We found no association between post-surgical persistence of epileptic seizures and depressive psychopathology. Severe mental disorders following epilepsy surgery occurred in two distinct presentations: hyper-acute, short-lived severe syndromes that occurred in the first 4 weeks post-surgery, with psychotic symptoms, dysphoria and suicidal or homicidal ideation (3 cases); late psychotic syndromes with insidious development more than 12 months after surgery (3 cases, two of them with no previous history of mental illness), with predominantly depressive psychotic symptoms. We found no association between the former and the latter cases. One of the immediate post-surgery cases had a history of psychosis prior to the surgical intervention. All three cases developing in the immediate post-surgery period had been submitted to left Hippocampectomy plus amygdalectomy (χ2=3.34; p=0.067). These patients were also younger than the remaining sample (32±3 vs. 43±14.6, t=2.3; p=0.043). Two of the 3 cases with pre-surgical psychotic syndromes remitted after surgery. Conclusion The relation between psychopathology and surgical treatment of epilepsy is difficult to establish or to predict, and differs amongst individuals. Literature shows that anxiety/depressive disorders are the most frequent psychopathologic occurrence in all post-surgical phases; that previous existence of psychopathology predicts its occurrence within a year from surgery; and that in some patients surgery was followed by epilepsy remission and previous psychopathology. In contrast with some of the previous literature on this subject, we observed that the type of intervention influences psychopathology evolution; and that hippocampectomy plus amygdalectomy is associated with higher incidence of psychopathology within a year from surgery. Left-hemisphere intervention may be associated with a higher risk of late depression, which is in line with the results of the abundant research on the relation between left-hemisphere lesions and depressive psychopathology. On the contrary, hippocampus sparing may have protecting effects in what concerns post-surgical psychopathology. The first four weeks seem to be a risk period for the occurrence of severe hiper-acute psychopathology, an observation that has not been described in literature. Such syndromes are unsystematized, self-limited, and potentially dangerous. Their occurrence is difficult to predict, in spite of the possible association with more extensive interventions (hippocampectomy plus amygdalectomy) and younger age. Conclusions are limited by small sample size. The incidence of late psychopathology may have been overestimated due to referral bias. It seems advisable that epilepsy surgery patients without psychopathology are observed in neuropsychiatry at least twice within a month from surgery, monthly within a year, and at least every six months after the first year.