Objectives: To compare the efficacy and safety of four atypical antipsychotic drugs with each other (aripiprazole, risperidone, olanzapine, quetiapine) in the treatment of delirium, with patient__ampersandsignrsquo;s age taken into account. Methods: This study was a 7 day prospective, comparative clinical study of efficacy and safety among four atypical antipsychotics in the treatment of delirium at a tertiary care hospital in central India. The patients with symptoms, suggestive of delirium were confirmed for diagnosis and treatment was started, after enrolling them in this study by the department of Psychiatry. A total of 70 subjects were allotted to receive either aripiprazole (n=20), risperidone (n=19), olanzapine (n=16) or quetiapine (n=15). The efficacy was evaluated by Delirium Rating Scale (DRS) - Revised 98 and safety by Udvalg Kliniske Undersogelser (UKU) side effect rating scale. Results: At baseline, the differences in mean DRS scores and the rates of improvement among the four groups were not statistically significant. The treatment response was comparatively lower in patients older than 70 years, than patients below 70 years age and this effect was similar in all four study groups. Seventeen patients had few adverse effects, but no significant differences in terms of adverse effects were found between four groups. Conclusion: Aripiprazole, risperidone, olanzapine and quetiapine showed same efficacy and safety profile in treating delirium patients. But, from our findings, it can be inferred that age factor needs to be considered critically, while administering any antipsychotic drug.