Hospitalized patients with persistent pain are among the most challenging populations to effectively manage because of coexistence with acute pain. Nurses play a vital role in pain management; however, gaps in knowledge and detrimental attitudes exist. The purpose of this study was to evaluate the effectiveness of a targeted evidence-based pain education program to increase nurses’ knowledge and attitudes about pain management. One group, paired, pretest/posttest educational intervention. A convenience sample of nurses from three medical and surgical inpatient units were recruited. Participants completed a pretest, the Knowledge and Attitudes Survey Regarding Pain Scale, to assess education needs. Identified gaps were targeted during program design. The program consisted of two 30-minute interactive educational sessions approximately 1 month apart. The first session, delivered by a pharmacist, covered pharmacology and pathophysiology content. The second session, delivered by trained registered nurses, used case studies paired with video scenarios. A total of 51 nurses completed the pretest. The final sample consisted of 24 nurses who completed both the pretest and posttest. The mean age was 30 years; 88% were female, and 92% were baccalaureate prepared. Paired t tests indicated higher posttest total scores (p < .001) after the education program compared with pretest scores. Overall program satisfaction was positive. This study found improvement in persistent pain management knowledge and attitudes among direct care nurses caring for hospitalized patients. A targeted educational program may be an effective and efficient delivery method.