The delivery of targeted temperature management (TTM) is recommended for cardiac arrest patients with specific initial rhythms after the return of spontaneous circulation. Some hospitals have established institutional TTM protocols based on national guidelines. Yet, successful implementation of an institutional TTM protocol depends on the nurses’ knowledge and skills. The study’s purpose was to compare the level of post-training knowledge, psychomotor skills, confidence and satisfaction among nurses taught the delivery of TTM with video lecture versus high fidelity simulation. The effectiveness of the two different training programs was compared with multiple choice and psychomotor skills testing prior to, immediately after, and 6 weeks after training. Confidence and satisfaction were assessed using a questionnaire immediately after training and 6 weeks later. Mixed effects model and independent t-tests were used to investigate the study aims. The results from the mixed effects model, repeated measures analysis of variance, simple regressions and paired t-tests were all consistent. Fifty-two nurses were recruited; all completed baseline and immediate post-intervention testing, while 48/52 (92.3%) completed follow-up evaluation at 6 weeks. The knowledge test scores did not differ between the groups immediately after the training (beta = 3.80, SE = 3.47, p = .27), but there was a strong trend 6 weeks after training, with higher scores in the simulation group (beta = 7.93, SE = 3.88, p = .04). In the simulation group, skills were significantly better immediately after the training, however, there was no significant difference between the groups 6 weeks later. No difference in confidence was found between the groups at either post-test point. Training satisfaction was significantly higher in the simulation group at both post-testing points. Nurses trained with high-fidelity simulation may benefit from such training by maintaining their TTM knowledge longer. Frequent “booster” sessions may help to maintain their competency in the use of cooling equipment. Further research should focus on the assessment of the effect of different TTM education interventions on the transfer of the knowledge/skills to bedside and subsequent patient outcomes.