This study is an 18-month, single-group, open-label (name of study drug is known to patients), multicenter study to evaluate the safety, tolerability and treatment response of paliperidone palmitate administered as once-monthly injections to patients with schizophrenia who previously received treatment with oral antipsychotic medications. A target of 587 patients (inpatients or outpatients) with schizophrenia will be enrolled in the study and will receive, without cost, injections of study drug (paliperidone palmitate) on Days 1, 8, 38, and thereafter at one-month intervals up to 18 months. Enrollment in the study will be limited to patients who are diagnosed with schizophrenia within the past 5 years. The study will consist of a screening period of up to 5 days before treatment, an 18-month treatment period, and an end-of-study or early withdrawal visit approximately 30 days after the last injection of study drug. During the screening period (after patients have provided signed informed consent to participate in the study), information will be collected regarding the patients medical and psychiatric history, demographics (age and race), current symptoms of the patients schizophrenia, and whether or not the patient would like to sign an additional informed consent form to participate in the pharmacogenomic (the study of how genes affect a person's response to drugs) component of the study that involves the collection of one 10 ml blood sample (equivalent to about 2 teaspoons of blood). During screening, entry criteria for the study will be reviewed and a physical examination performed. Patients will also be asked questions about the types of healthcare resources (institutionalizations/hospitalizations, emergency room visits, etc) they utilized during the previous 12 months however, this information is optional and its collection will depend upon the availability of the data. Patients who are currently receiving treatment with any oral antipsychotic medication must discontinue the use of the medication by Day 1 of the study. If the patient was receiving a high dose of an antipsychotic medication or was also receiving an anticholinergic medication (a drug that prevents involuntary muscle movements associated with the use of antipsychotic drugs in the treatment of schizophrenia), the investigator may decide to have the patients dose of antipsychotic (and/or anticholinergic) medication tapered (gradually reduced) to discontinuation beginning on Day 1. The patients time to taper-off the previous antipsychotic and/or anticholinergic medications will depend on the dose of the medication. Patients receiving anxiolytics (anti-anxiety drugs), mood stabilizers, anticholinergics, or antidepressants greater than 4 weeks before the screening visit will be allowed to continue taking these drugs. Upon meeting the entry criteria for the study, patients will receive a total of 19 intramuscular (IM) injections of paliperidone palmitate during the 18-month treatment period as follows: 150 mg equivalent (eq) on Day 1, 100 mg eq on Day 8, 75 mg eq on Day 38, and paliperidone palmitate injections of 50, 75, 100, or 150 mg eq once monthly on Days 68, 98, 128, 158, 188, 218, 248, 278, 308, 338, 368, 398, 428, 458, 488 and 518. Depending on the patients ability to tolerate a dose paliperidone palmitate, doses may be adjusted higher or lower every 30 days per the clinicians judgment within the dose range of 50 to 150 mg eq. If the patient reports any signs or symptoms of worsening of schizophrenia, the investigator may prescribe a rescue medication (quick-relief or fast-acting medications that usually work right away to relieve symptoms) such as lorazepam (an antianxiety drug) to control agitation, irritability, restlessness, and hostility. The investigator may also prescribe an anticholinergic medication to treat involuntary movement disorders if observed in patients. All prescription and over-the-counter medications taken by patients during the study are to be reported. At the end of the 18-month treatment period, all patients will complete an end-of-study visit (or early withdrawal visit for patients who do not complete the study) to have a physical examination performed, laboratory tests (including a urine pregnancy test for women of childbearing potential) performed, vital signs measured, and information collected regarding the occurrence of adverse events and the use of medications other than study drug from the time of the previous study visit to the end-of-study (or early withdrawal visit). The primary objective of the study is to evaluate safety, tolerability and treatment response of once-monthly injections of paliperidone palmitate measured by the use of a Positive And Negative Symptom Scale (PANSS). The safety and tolerability of once-monthly injections of paliperidone palmitate administered to patients with schizophrenia will be evaluated during the study by monitoring adverse events, findings from clinical laboratory tests (serum chemistry including lipids), vital sign measurements (blood pressure, pulse rate, and weight), physical examinations, and movement disorder evaluations using the Extrapyramidal Symptom Rating Scale \[ESRS-A\]). All clinically significant abnormalities in patients that persist at the end of the study will be followed by the Investigator until resolution or until a clinically stable endpoint is reached. Treatment response will be evaluated 5 times during the study (Visits 2, 4, 6, 8 and 10) by findings obtained from the PANSS (a 30-item questionnaire that is administered to the patient by a qualified person \[ie, rater\] to measure the presence/absence and severity of positive and negative symptoms of schizophrenia. In addition to the safety, tolerability, and treatment response data collected, patients who volunteer to participate in the pharmacogenomic component of the study will have one 10 ml sample of blood collected at on Days of Visit 2. If a replacement blood sample is needed for the pharmacogenomic component of the study, the patient will need to sign an additional informed consent form. Patients will receive a paliperidone palmitate intramuscular (IM) injection of 150 mg equivalent (eq) on Day 1, 100 mg eq on Day 8, and 75 mg eq on Day 38.Thereafter, patients will receive once monthly IM injections of 50, 75, 100, or 150 mg eq of paliperidone palmitate. Doses may be adjusted every 30 days per the clinician's judgment within the dose range of 50 to 150 mg eq.Patients will receive a total of 19 injections of study drug over an 18-month treatment period.