Background: Drug-resistant tuberculosis (DR-TB) remains one of the major public health problems in many countries around the world. The second-line TB treatment regimen for patients with DR-TB consists of several drugs. In addition to Bedaquiline, several other drugs such as Moxifloxacin, Levofloxacin, Clofazimin, and Delamanid are known to cause side effects such as QTc interval prolongation. Aim. To determine the effect of non-Bedaquiline regimen therapy in patients with DR-TB on QTc interval prolongation. Methods: This study is a retrospective cohort study that analyzed the medical records of 50 DR TB patients who underwent treatment from January 2023 to November 2024 at Labuang Baji Regional General Hospital, Makassar. Results: Of the 50 study samples, 27 (54%) subjects had QTc interval prolongation. Post-hoc analysis showed significant differences between baseline and measurements at month 7 (p=0.002), month 8 (p=0.001), and month 9 (p=0.017), but not significant at month 10 (p=0.137). There was no statistically significant association between age (p=0.531), gender (p=0.054), diabetes mellitus (p=0.585), obesity (p=0.674) on QTc interval prolongation. Patients receiving the combination of Levofloxacin-Clofazimin-Linezolid-Cycloserine (Lfx-Cfz-Lzd-Cs) was the most commonly used regimen in the group with QTc prolongation (25.9%) although not statistically significant (p=0.853). Even though a higher proportion of women showed QTc prolongation, it was not statistically significant. Conclusion: This study shows that non-Bedaquiline MDR-TB regimen therapy provides a significant and dynamic QTc interval lengthening effect during the 4-month treatment period.