Neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be relatively persistent towards psychopharmacological interventions. There are hints that atypical antipsychotics can influence neurocognitive dysfunctions more favorable than conventional compounds. But little is known about differences in efficacy on neurocognitive dysfunctions linked to the variety of receptor profiles of different atypical antipsychotics. This study compared the effects of the atypical antipsychotics quetiapine and olanzapine on cognitive function in patients with an acute episode of schizophrenia. Patients were randomized to receive quetiapine or olanzapine for 8 weeks. Cognitive function was assessed at baseline, week 4 and week 8. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Improvement Scale (CGI). Tolerability was assessed each week using the Extrapyramidal Symptom Rating Scale (ESRS), the Barnes Akathisia Scale (BAS) and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). In total, 52 patients were enrolled in the study. Data from the 33 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 4 and Week 8) are analyzed here. Both quetiapine and olanzapine improved global cognitive index z-scores, however, this was more marked with quetiapine. Between-group comparisons showed significantly greater improvements in reaction quality/attention with quetiapine than olanzapine. Quetiapine and olanzapine produced significant improvements from baseline to week 8 in PANSS total and subscale scores. Both treatments were well tolerated, especially no EPS occurred during 8 weeks of treatment. Both quetiapine and olanzapine improved cognition; however, the improvement in cognitive index scores was more marked in patients receiving quetiapine. Furthermore, quetiapine produced a significantly greater improvement in reaction quality/attention than olanzapine.