Background: Health education is the means by which professional knowledge is improved. In this context, the combination of multimodal educational strategies must be implemented and evaluated to verify their impacts on the adherence of professionals working in coronavirus disease 2019 (COVID-19) care sectors, especially in a pandemic scenario. Objectives: This study aimed to evaluate self-reported adherence to standard precautions (SP) among nursing professionals before and after a multimodal educational intervention. Methods: This quasi-experimental study was carried out before and after the multimodal educational intervention within February and June 2022. The intervention comprised three educational strategies, previously published separately: the use of a composite of five moments for educational construction, a validated educational video, and a problematizing discussion with the use of a quiz (true or false), focusing on questions with the lowest correct rate (cut-off < 70%) in phase 1 of data collection. The study involved 99 nursing professionals from a large hospital in the Brazilian Midwest. This study used a sociodemographic characterization instrument and the Compliance with Standard Precautions Scale (CSPS) to assess adherence to SP. The scores before and after the intervention were represented with mean and standard deviation. The Wilcoxon test, Mann-Whitney test, Kruskal-Wallis test, and Kolmogorov-Smirnov normality test were performed using SPSS software (version 20.0). Results: The sample comprised 99 participants, predominantly female (85.9%), working in various departments, including inpatient units, hemodialysis, intensive care unit (ICU), emergency room, and others (not specified). There was a statistically significant difference between the scores before (15.29 ± 2.23) and after (16.48 ± 1.98) the educational intervention (W = -4.443; P < 0.05). Additionally, there was a statistically significant increase in adherence after the intervention concerning the correct disposal of sharps boxes (P = 0.023) and changing out of uniforms in designated areas (P = 0.034). Conclusions: The obtained results demonstrated, in a pioneering manner, that the use of a multimodal educational strategy (combining different approaches such as the use of five moments, a validated video, and a question-and-answer quiz) had a positive impact on adherence by professionals who work in sectors caring for patients with COVID-19.