Objectives: To determine the incremental cost-utility ratio (ICUR) and incrementalcost-effectiveness ratio (ICER) of paliperidone palmitate in the maintenance phase ofschizophrenia compared to other antipsychotics available in Colombia. Methods:Cost-utility and Cost-Effectiveness analysis, from the perspective of the third-partypayer, considering the quality-adjusted life-years (QALYs) and avoided relapses,respectively, with the use of paliperidone palmitate long-acting injection (LAI). AMarkov model was used over a time horizon of five years. The selection of the initialand alternative treatment was determined from a literature review, patterns of useof antipsychotics in five psychiatric centers in Colombia, and the recommendationsof medical experts consulted through an advisory board. The selected alternativeswere: paliperidone palmitate LAI, quetiapine oral, risperidone LAI, olanzapine oraland risperidone oral. Direct medical costs were considered: antipsychotic therapy,support and medical monitoring, handling crisis and relapse or subsequent treatmentphases (what is meant by lines?). A sensitivity analysis on prices and the keyvariables (Average length of stay per hospitalization, adherence, risk of relapse ofthe model was) performed. Results: The expected costs of care (USD) were: $11.411with paliperidone palmitate LAI, $8.491 with quetiapine oral, $4.367 with olanzapineoral, $5.540 with risperidone oral and $12.623 with risperidone LAI. The ICUR of paliperidonepalmitate was, expressed in USD per QALY, $18.349 compared to quetiapineoral; $36.677 compared to olanzapine oral; $21.970 compared to risperidone oraland dominant in relation to risperidone LAI. The ICERs of paliperidone palmitatewere expressed in USD per relapse avoided, $5.682, $18.057, $7.837 and dominant,compared to quetiapine oral, olanzapine oral, risperidone oral and risperidoneLAI, respectively. The results showed a reduction in total relapses. Conclusions:The treatment of schizophrenia during the maintenance phase with paliperidone palmitate, presents a lower expected cost than that obtained with risperidone LAIand increased QALYs.