Flipped classroom pedagogy, an alternate to lecture instruction, shifts the focus of student learning from passive to active by facilitating a student-centered classroom environment. When coupled with the innovative uses of educational technologies, instructional delivery and design can be enhanced, thereby impacting student academic performance. Active learning encourages students to construct and apply their own knowledge through active participation in the learning process and collaboration with others in the classroom (Mostrom & Blumberg, 2012). Nursing education regulatory agencies stress implementation of active pedagogical practices and student-centered classroom environments to prepare graduates with essential knowledge and professional skills to practice (Everly, 2013). However, in nursing programs, traditional lecture instruction is repeatedly utilized and argued to be an ineffective approach for students to attain high academic achievement. Additionally, there are concerns that graduate nurses are inadequately prepared with the acquisition of fundamental knowledge of pharmacology and application for safe nursing practice (McLaughlin et al., 2014). The purpose of this quantitative, quasi-experimental study was to determine if flipped classroom pedagogy compared to traditional lecture instruction improved academic performance, thus increasing students’ depth of knowledge. The experimental sample included 38 students enrolled in two sections of an associate degree nursing pharmacology course during a summer semester, who received flipped classroom instruction for three of the six modules. Also, 42 students, in two sections from the prior summer term, served as the control group and were entirely taught with traditional pedagogical instruction. Multivariate analysis of variance (MANOVA) between factors indicated no significant difference in academic performance when comparing the six unit exam and final exam grades of both samples. However, analyzing examination scores of the experimental group after flipped instruction was implemented in three of the six modules, utilizing analysis of variance (ANOVA) repeated measures with covariance, revealed a significant difference on exams in which the participants were instructed with flipped instruction. The study findings suggest flipped classroom pedagogy should not be overlooked as an instructional method effective for nursing pharmacology education; however, the dearth of conclusive evidence on this pedagogical practice indicates further research is needed.