Objective: Although the effectiveness and adverse effects of long-term therapy are still mostly unknown, patients are increasingly using and seeking LT4/LT3 combination treatment for persistent hypothyroid symptoms. The purpose of this study was to assess the quality of life (QoL) and hypothyroid symptoms of the patient group that was affected by LT4/LT3 in a long-term manner. Methodology: A cross-sectional study of 66 hypothyroid patients who had starting LT4/LT3 combination medication earlier was conducted. The patients were divided into two groups based on their current treatment: T3 responders, who were still getting LT4/LT3 treatment, and T3 non-responders, who had stopped LT3 treatment since it was not working. Hypothyroid symptoms were measured using a validated symptom score, and QoL was assessed using ThyPRO. The article presents a real-world study that shows dissatisfied people being treated at an outpatient clinic. Results: The subjects started LT4/LT3 combination therapy 5.4 years ago, and their median age was 56. Twelve patients stopped LT3 treatment because it was ineffective, whereas fifty-four patients remained to undergo LT4/LT3 therapy. The QoL of the patients in the T3 responder group was similar to that of the background population. Remarkably, the T3 responder group's symptom scores were comparable to those of Nepalese women with overt hypothyroidism. In the T3 responder group, 38% of patients had thyroid stimulating hormone (TSH) levels below 0.4 mU/L, which suggests over-treatment. Conclusion: Patients still had numerous symptoms even though LT4/LT3 medication was well-tolerated, had no adverse effects, and had a great quality of life.