Purpose <p>Over- and undertreatment of chronic diseases are common. In this context, real-world data on the use of levothyroxine are limited. The aim was to determine the patterns of use, persistence, effectiveness, safety, clinical inertia, and adherence related to levothyroxine treatment in a group of patients with thyroid disease in Colombia.</p> Materials and methods <p>This was an observational study of patients treated with levothyroxine. Clinical records were reviewed, and the minimum patient follow-up was one year. Descriptive, bivariate and multivariate analyses were performed.</p> Results <p>A total of 398 patients were identified; the median age was 53.5 years, and 71.1% were women. A total of 76.9% of the patients received levothyroxine for clinical hypothyroidism, and few adverse events occurred (4.3%). 52% of the patients were not on goal at their first thyroid-stimulating hormone (TSH) checkup. Only 36.4% had a second TSH control appointment, but among them, 65.1% did not reach their goals; moreover, 31.7% demonstrated clinical inertia. The medication possession ratio was 66.8% (≥ 80%: 31.4%), and 47.7% of the patients showed persistent use at one year. The presence of adverse events was associated with a lower probability of persistent use (OR:0.16; 95%CI:0.04–0.64).</p> Conclusions <p>Clinical inertia and poor disease control were common, whereas rates of adherence to and persistence with levothyroxine treatment were low. However, patients aged ≥ 40 years, those with a high educational level and chronic comorbidities, and those who habitually attended TSH control appointments were more likely to be persistent with their treatment at the one-year follow-up.</p>