Prochlorperazine maleate, a well known antiemetic is used in the treatment and prevention of nausea and vomiting. The dosage of the drug is usually 5 or 10 mg thrice or four times a day, because of its short biological half life (6-8 hours). The bioavailability of drug is 12.5%. Due to the solubility of drug in acidic pH, the drug is absorbed rapidly from stomach. Present study was aimed to formulate and evaluate effervescent floating matrix tablets of Prochlorperazine maleate. Hydroxyethyl cellulose HHX (Natrosol HHX) and hydroxypropyl cellulose (HPC-H) were used as release retarding agents. Sodium bicarbonate and citric acid were used as gas forming agents. Floating tablet of prochlorperazine maleate was prepared to enhance the bioavailability of drug, to prolong the gastric retention time (GRT) and to reduce the frequency of administration. The formulations were prepared by direct compression method. The tablets were evaluated for pre-compression and post-compression parameters. 32 full factorial designs were used to optimize the concentration of release retarding agents. From the factorial batches, formulation H7 containing 70% of hydroxyethyl cellulose HHX and 12% hydroxypropyl cellulose - H was found to be the optimized batch. Formulation H7 followed Korsmeyer Peppas release kinetics, with sustained drug release of 93.64±6.4 % and floating for 10 hours. In-vivo X-ray placebo study of optimized batch (H7) showed retention of tablet in stomach for 6±0.5 hours. Thus, the study proved the successful floating delivery of drug in stomach. © 2016 Bentham Science Publishers.