Several treatments are available for the treatment of acute manic and mixed episodes associated with bipolar disorder. Some of these treatments although used for many years, are associated with well-known problems such as poor tolerability, significant toxicities, narrow therapeutic ranges, and drug interactions. Often, several drugs must be used in combination to achieve the best clinical effect. More recently, a group of compounds known as atypical antipsychotics, such as risperidone, have been licensed for use in this indication. Based on the pharmacological profile of Paliperidone, it is expected to be effective in the treatment of acute manic and mixed episodes associated with bipolar disorder. Paliperidone extended release has been shown to be effective in schizophrenia and it has an improved drug delivery system with a reduced potential for drug interactions. Study drug tablets are designed to deliver the appropriate amount of drug (3 mg or 6 mg) using a "Push-Pull" delivery system based on a patented oral osmotic pump technology (OROS) that allows the drug to be delivered at a relatively controlled rate for 24 hours. This study will test 3 different doses of paliperidone extended release (3, 6, or 12 mg/day once daily) compared to placebo (inactive substance). There are 3 parts to the study: a screening and washout phase that lasts up to 7 days to determine if patients are eligible for the study and to discontinue all current medications, a double-blind treatment phase that lasts for 3 weeks, and a follow-up phase that lasts about 1 week after the end-of-study visit or early withdrawal from the study. During the double-blind treatment phase, patients are randomly assigned to receive treatment either with placebo or 1 of 3 daily doses of paliperidone extended release. Patients assigned to paliperidone extended release will receive either 3, 6, or 12 mg/day given once daily for a 3-week period. All patients whether receiving paliperidone extended release or placebo will take 2 capsules each time the study drug is given. Patients will be hospitalized for at least the first 7 days of double-blind treatment, and may be discharged on the seventh day and followed as outpatients based on the judgment of the study doctor. End-of-study/early withdrawal procedures will be done after the last dose of study drug has been received and blood samples have been taken, or at early withdrawal from the study. Patients will have a follow-up visit with safety evaluations approximately 1 week later. The study, including the screening and washout phases, will last approximately 35 days or 5 weeks. Effectiveness will be primarily determined by the change in the total Young Mania Rating Scale (YMRS) score from the beginning (baseline) to the end of the double-blind treatment phase of the study. The Young Mania Rating Scale is an 11-item established measure used to evaluate manic symptoms. A secondary measure of effectiveness is the change in the Global Assessment of Functioning Scale (GAF) from baseline to the end of the double-blind treatment phase of the study. Other measures of effectiveness include the time to onset of therapeutic effect, responder rate (defined as 50% or more reduction from baseline in Young Mania Rating Scale score), and changes from baseline to the end of the double-blind treatments phase in all other assessment scales. Additional assessment scales will be used to evaluate the clinical progress of the patient, psychotic and depressive symptoms in bipolar disorder, quality of sleep and daytime drowsiness, health-related function, and rate the severity of the patient's bipolar disorder. Safety will be evaluated by the frequency, severity, and timing of side effects, clinical laboratory tests (including pregnancy tests), 12-lead electrocardiograms (ECGs), vital signs measurements, and physical and neurological examinations. The study hypotheses for the primary and secondary effectiveness measures are 1) that at least 1 dose of paliperidone extended release is better than placebo on the change from baseline in the Young Mania Rating Scale total score at the end of 3 weeks of treatment, and 2) at least 1 dose of paliperidone extended release is better than placebo on the change from baseline in Global Assessment of Functional Scale score at the end of 3 weeks of treatment. The potential effect of the variation in genes related to paliperidone ER may be evaluated separately in patients who consent to DNA (deoxyribonucleic acid) testing. Paliperidone ER, 3, 6, or 12 mg/day or placebo once daily for 3 weeks. To maintain the blind, all patients will take 2 capsules each time study drug is given. Capsules may contain a 3-mg tablet and matching placebo, a 6-mg tablet and matching placebo, two 6-mg tablets, or placebo (inactive) tablets. The doses of study drug will be fixed throughout the study.