Background It is unknown whether nurses' knowledge about pain among patients with sickle cell disease (SCD) reflects the current standard of care. The authors evaluated changes in nurses' knowledge and simulated practice behavior after a continuing education program. Method Inpatient nurses completed an e-learning program on SCD pain; a pretest and a posttest with the same 10 questions; and two patient cases with four pain intervention options at the posttest. Results On the pretest, the mean percentage of correct answers was 83% (SD = 13%). The mean percentage of correct answers increased by 12% (p < .0001) on the posttest. For the first simulated patient case, 100% (n = 31) of the nurses selected an appropriate pain intervention option based on the patient-reported pain score. For the second simulated patient case, 84% (n = 26) did so. Conclusion Increased knowledge does not always translate into simulated practice change. The reasons for this are unknown, but they could include implicit bias from exposure to patients who have high use of acute care, although the minority of patients with SCD fit this description. [J Contin Educ Nurs. 2022;53(3):137-144.].