External quality assurance schemes (EQAS) are invaluable tools used by medical laboratories to assess the performance of their testing systems. EQA is an exercise conducted by the EQA provider to compare the testing performance of a laboratory with other laboratories, identify areas of improvement and provide insights into laboratory quality standards. This retrospective study evaluates the continuous improvement of the CMC EQAS Clinical Biochemistry program and the benefits of the program to the overall performance of the Indian medical laboratories over the last four and a half decades in terms of the increase in participants, programs, analytes, lab types, lab sizes, and performance. The CMC EQAS program with 50 participating laboratories in 1978, increased to 13,883 laboratories in 2024, with increase in programs and analytes. 70% of the participating laboratories received < 100 patient samples/day. The percentage of laboratories switching over to better methods for the analytes increased, improvement in the interlaboratory comparison was reflected by a decrease in % CV and an improved performance of labs as shown by an increase in the percentage of laboratories with an SDI score of < 2. In conclusion, the establishment of the CMC EQAS program over the past four and a half decades through the distribution of in-house prepared lyophilized quality control material is a useful scheme to monitor the performance of clinical chemistry laboratories in India. This study highlights an increased awareness towards the concept of quality control and thus an overall improvement in performance in the Indian medical laboratories.