Introduction Innovating strategies have become a compulsion in all fields associated with improved outcomes. Similarly, an innovation was introduced in the curriculum design and content to be tested for the Anatomy and Physiology course at the College of Science and Health Professions (COSHP), King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), in the spring semester of 2020. Before the COVID-19 pandemic, until the spring semester of 2019, two examinations were conducted as continuous assessments (Midterm I and II), followed by a comprehensive Final examination. In the spring semester of 2020, these examinations were replaced with Block I, II, and III examinations, respectively, with modified content and weightage. The Final examination was comprehensive and included 24 Anatomy, 21 Physiology lectures, and three case-based learning (CBL) sessions, whereas Block III included only eight Anatomy, seven Physiology lectures, and 1 CBL session. Midterm I and II weighed 20% each with a comprehensive examination of 35%, while Block I, II, and III were all 25% each. This study focuses on the impact of the curriculum modifications on the results of written examinations for preprofessional students enrolled at Riyadh, Jeddah, and Al-Ahsa campuses. Methods This retrospective study included data from 2356 male and female students from Riyadh, Jeddah, and Al-Ahsa. Data included Midterm I and II grades and Final examination grades for spring semester 2019 and Block I, II, and III examination grades for spring semester 2021. The results of the spring semester 2021 examinations were compared with the spring semester 2019 examination. The spring semester of 2020 was skipped to avoid the effect of online examinations during the COVID-19 restriction period. Data were analyzed using the statistical software SPSS version 23.0 (IBM Corporation, Armonk, NY, USA). Coefficient of variation (CV) compared spring semester 2019 and spring semester 2021 examination outcomes. The findings were analyzed concerning data related to gender, student groups, and campuses. An independent t-test of proportion was used to compare the CVs for spring 2019 and 2021. Results The overall comparison showed better results in the spring semester of 2021 (p-value < 0.01). Campus-wise, the results were significantly better for Riyadh (p-value < 0.01). The gender-wise study showed better performance from male students (p-value < 0.01). Concerning campus and gender, the results of male and female students of the Riyadh campus came out to be highly significant (p-value < 0.01). Conclusions Changing from Midterms to the Block system significantly improved the Block III examination results in spring semester 2021, particularly at the Riyadh campus. Overall, the changes remained helpful to all students. Further studies are needed to investigate the long-term effect of the curriculum changes.