Traumatic brain injury (TBI), particularly damage to the frontal lobes, often produces a specific configuration of behavioral and personality changes known as frontal syndrome. Recent data, however, indicate that patients, depending on whether the damage has occurred in the left or right hemisphere of the brain, manifest one of two profiles of this syndrome in which negative or positive behavioral disturbances predominate. The purpose of this study was to evaluate the differences in frontal syndrome profiles present in patients 20 years after injury to the frontal lobes of the right and left hemispheres. Material and methods The study included a total of 360 patients with brain injury confirmed by neuroimaging studies, rehabilitated at the Reintegration and Training Center of the Polish Neuropsychological Society. The subjects were matched by age and gender into 2 experimental groups: Group A, included 180 patients (including 90 men and 90 women) with post-traumatic frontal lobe damage in the left hemisphere of the brain, and Group B, which included 180 patients (including 90 men and 90 women) with post-traumatic frontal lobe damage in the right hemisphere of the brain. The study employed documentation analysis, clinical interview and the Frontal Syndrome Behavior Questionnaire (FBInv). In accordance with the guidelines of this questionnaire, assessments were made based on an interview with the patient's caregiver in the absence of the patient. The study was conducted twice: two years (baseline) and about 20 years (follow up) after the brain injury. Results It was found that thepatients with left frontal lobe damage were characterised by significantly higher levels of so-called negative behavioural disorders overall and in the dimensions of apathy, passivity, indifference, concreteness, disorganisation, logopenia, apraxia of speech and perseveration, as well as significantly lower levels of loss of insight. While the patients with right frontal lobe damage were characterised by significantly higher levels of so-called positive conduct disorder overall and in the dimensions of hypersensitivity and irritability, excessive cheerfulness, unreasonable behaviour, inappropriateness and an absence of polite behaviour, aggressiveness, hyper-orality, hyper-sexuality, compulsivity, urinary and faecal incontinence and alien handedness. In addition, it should be noted that most of the recorded effects were found to be strong (η2> 0.14). The results indicated that 20 years after the brain injury, in terms of positive behavioural disorders overall, the group of patients with right frontal lobe damage showed a stronger decrease in disorders (η2= 0.64) over time when compared to patients with left frontal lobe damage (η2= 0.14). Conclusions We found that in the patients 20 years after post-traumatic damage to the frontal lobes is still manifesting frontal syndrome, however its profile is dependent on whether the damage occurred in the left frontal lobe or the right frontal lobe. The Frontal Syndrome Behavior Questionnaire can be used in the differential diagnosis of frontal syndrome after damage to the frontal lobes of the right and left hemispheres of the brain.