Introduction: Muslims find it difficult to take L-thyroxine on empty stomach during Sahur. Furthermore, physiological changes during Ramadan alter thyroid hormones level. Objective: To compare the efficacy, safety and patient’s preference of weekly vs daily dosing of L-thyroxine in Ramadan. Method: This is a pilot randomized open-label controlled trial among hypothyroid patients during Ramadan 2017-2018. Patients were randomized into weekly and daily arm. Weekly arm took 7x their usual L-thyroxine dose at least 30 minutes pre-sahur once a week while daily arm took their usual daily dose at least 2 hours after the last meal before bed. Thyroid hormones, lipid profile, cardiac parameters, cognitive and psychological function were assessed at baseline and at week 4. Cardiac reassessment was done within 24hrs after weekly dosing at week 2. Results: Eighteen patients were randomized into weekly and daily arm. Majority (66.7%) were hypothyroid secondary to radioiodine therapy. At the end of study, there were no significant changes of thyroid hormones level for weekly arm. However there was significant increment of TSH observed in daily arm [TSH w0 1.8(0.23,5.57) vs w4 3.65(0.45,16.1);p =0.011]. In terms of toxicities, there were no hyperthyroid or cardiac toxicities observed despite the significant increment of fT4 within 24hours of weekly dosing [fT4 w0 13.21(8.19,14.63) vs w2 17.43(12.38,22.55);p=0.011]. All patients were euthyroid and had no side effects. Majority (83.3%) of patients preferred weekly dosing during Ramadan. Conclusion: Weekly levothyroxine dosing during Ramadan appeared to be safe, efficient and the most preferred dosing method.