OBJECTIVES Medication satisfaction in subjects with schizophrenia may be related to efficacy and long-term adherence. This study evaluated medication satisfaction after treatment with paliperidone ER in subjects with a current suboptimal response to oral risperidone. METHODS A 6-week, prospective, international, randomized, blinded-initiation study. Inclusion criteria: schizophrenia per DSM-IV, treated with oral risperidone (4 or 6 mg/day) at least 4 weeks prior to entry, PANSS score ≥4 on ≥3 items (tension, unusual thought content, delusions, hallucinatory behavior, excitement, grandiosity or suspiciousness/persecution) and dissatisfaction with current medication (Treatment Satisfaction Questionnaire for Medication ≤3). Subjects randomized (1:1, blinded) to paliperidone ER 6 mg/day (optional increase to 12 mg/day) either immediately (6 weeks total) or delayed (continued risperidone for 2 weeks followed by paliperidone ER for 4 weeks). Primary end point for the overall group: change in Medication Satisfaction Questionnaire (MSQ) (1=extremely dissatisfied to 7=extremely satisfied) at week 6 end point. Additional end points: total PANSS and adverse events (AEs). Study ID: CR014347. RESULTS 201 subjects were randomized to immediate (n=100) or delayed (n=101) initiation of paliperidone ER. For the overall group, mean (SD) MSQ score improved significantly from 2.7 (0.8) at baseline to 5.1 (1.2) at end point (P<0.001). 82.7% of subjects were satisfied with their medication at end point vs 3.7% at baseline. Mean (SD) PANSS total score improved from baseline to end point (¨C12.9 [13.1]; P<0.001). At week 2, a higher percentage of subjects receiving paliperidone ER (immediate-initiation group) were satisfied with their medication compared with those still receiving risperidone (delayed-initiation group) (67.7% vs 45.3%; P=0.002). Most common AEs for overall group: insomnia (9.1%), constipation (7.6%), headache (7.6%) and somnolence (6.6%). CONCLUSIONS Schizophrenia subjects suboptimally responsive to risperidone reported improved medication satisfaction after 4 or 6 weeks of paliperidone ER.