The long term effect of post-partum thyroid dysfunction (PPTD) is not well established. This study was conducted to evaluate the outcome of permanent hypothyroidism and factors predictive of thyroid dysfunction in a large cohort of women with PPTD. In 164 women, treated with levothyroxine for moderate and severe post-partum hypothyroidism, the treatment was discontinued and subjects were followed-up for the recurrence of hypothyroidism. Factors such as thyroid function tests, tyroid peroxidase antibodies (TPOAb) titers, multiparity, history of autoimmune disorders, smoking habits, use of oral contraceptives, family history of thyroid disease, goiter size and age at active phase of PPTD were assessed. Seventy-one post-partum women without PPTD were considered as control group. One hundred forty-eight women (90%) returned for follow-up, and 93 subjects (63%) developed hypothyroidism with a median of 2 months after T4 withdrawal. Of factors predicting recurrence of hypothyroidism, only age, and serum TSH and T3 concentrations at the time of occurrence of PPTD entered the model in multiple stepwise regression analysis. Hypothyroidism occurred earlier and more frequently in women aged 30 and over, as compared to younger ones (p<0.01), hazard ratio 1.69. In 55 euthyroid subjects with history of PPTD, serum TSH was significantly increased as compared to the control group (3.0±1.6 vs 0.8±0.5 mU/l, p<0.001). These data, representing the largest cohort of women with PPTD who have been followed, show that a significant proportion of women with moderate and severe PPTD, in particular those aged 30 yr and over, develop recurrent hypothyroidism. Proper follow-up of all women with PPTD, the older ones in particular, is recommended.