BACKGROUND Incidence of Congenital Hypothyroidism in India is relatively high when compared to that of other parts of the world. The fact that only 5-10% can be diagnosed clinically signifies the role of screening program for early diagnosis and early initiation of therapy to treat this preventable cause of intellectual disability. Cord blood TSH (CB TSH) estimation has high sensitivity, but various maternal and perinatal factors affect the CB TSH levels, which may interfere with the interpretation. This study was done to find out the various maternal and perinatal factors affecting CB TSH level. MATERIALS AND METHODS A hospital-based cross-sectional study was conducted in the Department of Neonatology, Govt. Medical College, Ernakulam over a period of one year from February 2016 to January 2017. We enrolled 127 live neonates selected by systematic random sampling method. Cord blood TSH level was estimated and the results were statistically analysed with respect to various maternal and perinatal factors. RESULTS Mean CB TSH in the study population was 9.713 ± 7.286. The risk factors for a significantly high CB TSH level were low Apgar at 1 minute, Preterm babies and Primigravida mothers (p < 0.05). A significantly low CB TSH was noted in preterm neonates who received antenatal steroids (p < 0.05). The other factors like gestational diabetes, gestational hypertension, gender of the baby, birth weight and meconium stained liquor were found to have no significant relationship with the CB TSH level. CONCLUSION Mainly low Apgar at 1 min which is an indicator of foetal distress/ perinatal asphyxia, prematurity and parity contributed to the significant elevation of CB TSH level. Antenatal steroids can significantly blunt the TSH surge. Due consideration should be given to these factors while interpreting CB TSH levels.