Objectives To assess daytime cognitive performance, sedation and treatment satisfaction in patients with schizophrenia receiving quetiapine extended release (XR) versus quetiapine immediate release (IR). Methods Phase IV prospective, double-blind, crossover study (NCT01213836). Patients (N=66) with stable schizophrenia, treated with XR or IR before study start, were randomised (1:1) to treatment with XR followed by IR, or IR followed by XR, at the dose received before enrolment (400–750mg). After 10–16days on formulation 1, patients switched to formulation 2. Assessments from three post-dose visits (≥5days following treatment on each formulation) were analysed. Cognitive performance was measured by CogState Cognition testing. Sedation, treatment satisfaction and safety were also assessed. Results 65 patients received treatment (69.2% male; mean age 37.8years). Daytime cognitive functioning was similar for both groups; adjusted mean difference in Attentional Composite Score in XR and IR patients was 0.005 (p=0.907). Patients receiving XR were less sedated than those receiving IR, (Bond–Lader visual analogue scale score, mean [SD]: 23.5 [19.0] vs 28.6 [21.4]); estimated overall treatment difference: 5.2 (95% CI: 2.3, 8.2; p<0.0009). Patients receiving XR reported feeling less sedated than those on IR (Stanford Sleepiness Scale, mean [SD]: 2.4 [0.9] vs 2.6 [1.0]); estimated overall treatment difference: 0.28 (95% CI: 0.12, 0.43; p<0.0008). Patients reported improved overall treatment satisfaction (p=0.0417) and milder side effects (p=0.0035) with XR. Safety profile was similar in both groups. Conclusion Daytime cognitive performance was similar for both groups. XR was associated with less daytime sedation and improved patient satisfaction than IR.