Purpose: To determine the secular trend of the multiple birth rate in Korea from 1981 to 2017. Methods: This study used birth certificate data covering the years 1981-2017 (20,948,901 births), provided by Statistics Korea. The impact of assisted reproductive technologies (ART) on multiple birth was analyzed by examining data prior to and after the introduction of ART and the national support program for infertile couples in South Korea. The odds ratio (OR) and 95% confidence intervals were calculated to describe the secular trend in the multiple birth rate per 100 births. Results: During this period, the multiple birth rate per 100 births increased by 277 percent from 1.031 to 3.891, the twin birth rate increased from 1.013 to 3.807 (275%), and the triplet birth rate increased from 0.018 to 0.084 (363%). The secular trend of the multiple birth rate remained in the 1.000 level during 1981-1991, but has been rising steadily since 1992. The average increment of the multiple birth rate was 3.9% annually from 1981 through 2017 (peaking at more than 10 percent during 2006-2007). Prior to the introduction of ART in Korea (1981-1984), the multiple birth rate was 1.007, but after its introduction, the multiple birth rate was 1.005 in 1985-1989 (OR, 0.998; 95% confidence interval, 0.982-1.014), 1.084 in 1990-1994 (1.007; 1.060-1.094), 1.891 in 2000-2004 (1.894; 1.866-1.922), 3.127 in 2010-2014 (3.173; 3.129-3.217), and 3.811 in 2015-2017 (3.893; 3.835-3.952). Conclusion: Over the past three decades, multiple births have risen dramatically in Korea, primarily due to the increasingly widespread use of fertility therapies, and the delayed age of childbearing. There is a need for more research to understand the factors contributing to multiple births, and the national birth registration systems ought to be reformed to monitor whether multiple births originated spontaneously or from assisted-conception.