Purpose: Many factors are responsible for the occurrence of hypocalcemia after total thyroidectomy (TT). This study was conducted to look at the factors usually concerned in post TT clinically significant hypocalcemia (CSH). A scoring system is being developed in combination with these factors for early diagnosis of CSH. Study Design: Institution based Prospective study. Materials and Methods: Total 50 patients with benign goiter and early carcinoma thyroid were included in this study and all were go through total thyroidectomy. Age of the patients, pre-operative thyroid hormone status, serum Ca2+ level and 25 (OH) vitamin D were studied. Post-operative iPTH level at 8 hours and calcium level at 12 hours were measured. Condition of parathyroid gland and size of the nodule were studied and preserved during operation. CSH prediction score (0 to 8) was designed based on these 8 factors. Statistical Analysis: SPSS 16 software was used. Independent samples T-test and Chi-square test was used for comparison between two groups. P value __ampersandsignlt;0.05 was used as statistically significance. Results: There were 8 males and 42females. 64% (n=32) had euthyroid multi-nodular goiters, 24%(n=12) had toxic MNG, and 12%(n=6) had an early carcinoma of thyroid. 30%(n=15) developed CSH. CSH was developed in patients with low pre-operative serum calcium (P=0.000), low 25 OH vitamin D (P=0.001) with low serum calcium (P=0.000) at 10 hours, low post-operative iPTH at 6 hours (P=0.001), after surgery and lesser number of parathyroid identification at surgery (P=0.000)and nodule size (P - 0.000). Conclusions: Clinically significant hypocalcemia (CSH) after TT depends upon multiple factors and these factors (Hypocalcemia prediction score __ampersandsigngt; 3) can be taken account to predict it to discharge patients within one day after surgery.