Background: This study examined 5-year outcomes of patients prescribed risperidone longacting injection (RLAI) or aripiprazole in a clinical setting, using treatment discontinuation as a measure of effectiveness. Method: Patients who received RLAI or aripiprazole in the 18 months following their respective UK launches were included. Two-year outcome data were previously reported for these cohorts; this study reported an additional 3 years of follow up for each group. Data were collected from pharmacy records and by retrospective case note review. Patients were classified as continuers or discontinuers at 5 years and reasons for treatment discontinuation noted. Results: The number of patients remaining on treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI and aripiprazole respectively. Two patients treated with RLAI and three treated with aripiprazole were lost to follow up. Therefore, 5-year outcome data were available for 50 patients. Fifteen patients from each group were continuers at 5 years. Of these, four receiving RLAI and three receiving aripiprazole were coprescribed other antipsychotics at study endpoint. Reasons for discontinuation of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and patient death (n = 2; n = 0). Conclusion: There was no significant difference between the proportions of patients continuing RLAI or aripiprazole for 5 years. Continuation rates were relatively low (18% and 16% of the original RLAI and aripiprazole cohorts respectively), whilst coprescription of other antipsychotics at endpoint was relatively common. Lack of effectiveness was the most common reason for discontinuation of both compounds. These findings suggested that clinical effectiveness was somewhat disappointing, although the long period of follow up and number of patients previously treated with clozapine in the original cohorts were confounding factors.