The Serial Trial Intervention (STI) is a decision support tool to address the problem of underassessment and undertreatment of pain and other unmet needs of people with dementia. This study compared the effectiveness of the 5-step and 9-step versions of the STI using a two-group repeated measures quasi-experimental design with randomization of 12 matched nursing homes. The sample consisted of 125 residents with moderate to severe dementia. Both the 5- and 9-step STIs significantly decreased discomfort and agitation from pre- to posttest (effect sizes = 0.45 to 0.90). The 9-step version was more effective for comorbid burden and increased cortisol slope (effect sizes = 0.50 and 0.49). Process variables were all statistically significantly improved using the 9-step STI. Nurse time was not different between the two groups. The clinical decision support rules embedded in the STI, particularly the 9-step version, helped nurses change practice and improved resident outcomes.