Current trends in medical school education indicate an existing need for increasing medical student exposure to pharmacotherapy education. The objectives of this study are to describe the development of an interprofessional, application-based Pharmacotherapeutics in Primary Care selective for 3rd year medical students and to assess its influence on knowledge, attitudes, and skills related to pharmacotherapy of high-risk medications and patient populations. The selective was implemented across fourteen cohorts of medical students that were evaluated over a 5-year academic period (n = 68). Our curriculum was unique in that it merged basic pharmacology and pharmacotherapy concepts with application-based medication management of high-risk patients in addition to the incorporation of an interprofessional home visit experience. Pre- and post-assessment analyses found statistically significant improvements in students' pharmacotherapeutic knowledge and skills. There was a significant increase in the knowledge post-test mean score (71.8; SD = 11.2) compared to the pre-test mean score (57.3; SD = 11.9; P < .001). A similar trend was observed for the skills mean score in which the post-test average (63; SD = 16.9) was significantly higher than the pretest average (23.3; SD = 14.4; P < 0.001). Students' attitudes also improved when rating their confidence in completing specific tasks such as recommending dosing regimens and utilizing drug information resources. This intervention provided 3rd-year medical students with opportunities to improve their knowledge, attitudes, and skills related to the pharmacotherapeutic management of high-risk medications and patient populations while exploring meaningful interprofessional interactions with faculty and learners from other disciplines.