OBJECTIVE To study and compare the pattern of lipid profile changes in Thai HIV and tuberculosis (TB) co-infected patients after receiving two non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART). METHODS From an open label, randomized, comparative trial comparing treatment outcome between HIV and TB co-infected patients receiving nevirapine (NVP) or efavirenz (EFV) combined with stavudine and lamivudine, patient's body mass index (BMI), CD4 cell count, plasma HIV-1 RNA, fasting blood glucose, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were collected at baseline, 24, and 48 weeks of ART. RESULTS Of the 121 patients included in the present study, mean (SD) age was 36.9 (8.4) years and 66% were male. After 48 weeks of ART the median (IQR) percentage of TC, LDL-C, HDL-C and TG values were 21.1% (5.4-40.7), 23.5% (-0.8-49.8), 22.7% (0-50) and -1.0% (-34.6-32.2) respectively. The median (IQR) percentage change of the HDL-C value was significantly higher in NVP-based than EFV-based ART (31.9 [9.6-50.0] vs. 12.2 [-8.8-51.2]; p = 0.03). The proportions of patients with high TC (21.5%) and high LDL-C (29.2%) increased and low HDL-C (11.6%) decreased significantly at 48 weeks of ART compared to baseline (all, p < 0.01). The proportions of patients with high TC, high TG and low HDL-C were significantly higher in the EFV group than in the NVP group (p = 0.03 for high TC, p = .01 for high TG and p < 0.01 for low HDL-C). CONCLUSIONS NNRTI-based ART is associated with increases of TC, LDL-C and HDL-C values in Thai HIV and TB co-infected patients. More favorable lipid profile is observed in NVP-based than EFV-based ART.