BackgroundCognitive impairment is a major determinant of functional outcome in psychotic spectrum disorders. Among cognitive domains, motor response inhibition has received limited longitudinal investigation. The present study examined the temporal course of inhibitory performance and its relationship with dimensional psychopathology in schizophrenia and bipolar disorder. Methods Thirty-eight outpatients (23 schizophrenia spectrum, 15 bipolar spectrum) from the e-Prevention project were followed for up to 26 months. At monthly or bi-monthly intervals, participants completed a computerized Go/No-Go task assessing accuracy, response speed and intra-individual variability of response speed. Linear mixed-effects models evaluated the effects of time, diagnosis and longitudinal change in symptom severity on performance, controlling for medication and neuropsychological variables. Results Accuracy declined over time in schizophrenia but slightly improved in bipolar disorder, indicating divergent longitudinal trajectories (F = 9.02, p = .007). Time had no effect on response speed and intra-individual variability of response speed in either group. Increased positive symptom severity was associated with reduced accuracy in bipolar disorder but not in schizophrenia (F = 4.85, p = .036). Finally, greater speed intra-individual variability of response speed correlated with higher disorganization scores across diagnoses (F = 5.54, p = .027). Conclusions This study provides preliminary evidence that inhibitory control exhibits distinct temporal patterns in schizophrenia and bipolar disorder. Schizophrenia could be marked by gradual accuracy decline, while in bipolar disorder, accuracy may show relative stability modulated by positive symptoms. Future work on larger samples should incorporate neurophysiology/neuroimaging, to elucidate the underlying neural mechanisms of these differences.