We assessed the effectiveness of switching from paliperidone palmitate (PP) or risperidone long-acting injection (RLAI) to aripiprazole lauroxil (AL). Prospective, 6-month study in patients with schizophrenia with residual symptoms or intolerance with PP/RLAI. Effectiveness assessed via all-cause and medication-related discontinuation; CGI-S/BPRS and adverse event monitoring assessed efficacy/tolerability, respectively. Fifty-one patients (n = 50 PP; n = 1 RLAI) enrolled; 35 completed the study. All-cause and medication-related discontinuation was 30% and 9% over 6 months, respectively. CGI-S/BPRS improved significantly in those continuing treatment. Adverse events were generally mild to moderate. Patients with efficacy or tolerability concerns with PP/RLAI can be switched to AL.