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Introduction: The Self-Directed Learning (SDL) approach is an important component of the Competency-Based Medical Education (CBME) curriculum. However, learning independently can be challenging, even for the brightest and most motivated students. Moreover, self-evaluation is quite difficult. If SDL is used in combination with formative assessment and constructive feedback for individual topics, it would facilitate self-modulation by learners and guide them towards higher academic achievement. Aim: To compare the academic performance of first-year medical students in Anatomy Practical class using SDL with formative assessment and feedback versus conventional teaching methods. Materials and Methods: A comparative evaluation was conducted using a longitudinal study design in the Department of Anatomy, Medical College Kolkata, West Bengal, India, from November 2022 to June 2023. During Anatomy Practical classes, 250 first-year medical students, (Batch 2022-2023), were divided into two equal groups using simple random sampling through a lottery method. One group (study group) was taught by implementing SDL followed by formative assessment with immediate feedback, and the other group was taught by the traditional method (control group). Following the completion of each of the first three consecutive regions (superior extremities, inferior extremities, and thorax) during Anatomy Practical classes, summative assessments were conducted. The collected data were calculated in an Excel sheet and computed using JAMOVI software (free version). Independent t-test statistics for the three summative assessments were evaluated, and the p-value of each assessment was determined. A p-value <0.05 was considered to be statistically significant. Additionally, students' feedback was documented and analysed. Results: It was observed that there was an improvement in academic scores in both groups. However, higher academic performance was progressively attained in the group which was provided SDL sessions and formative assessment with immediate feedback. A total of 55 (80%) students passed the third summative assessment in comparison to 40 (59.7%) students of the control group who passed the same exam. Differences between the means of the control and study group were found to be statistically significant (p-value≤0.001 and 0.023 in two summative assessments). Conclusion: The present study revealed that SDL with formative assessment followed by immediate feedback during Anatomy Practical classes had a remarkable positive impact on students' academic performance compared to those students taught using conventional teaching methods and might be implemented in the future for better learning and improved academic achievement of students. [ABSTRACT FROM AUTHOR]