Background The Ministry of Public Health (Thailand), MoPH, has had a program called National Access to Antiretroviral Program for People who have AIDS (PHA) or “NAPHA”, to offer free antiretroviral drugs (ARV), which are locally produced in Thailand, to any HIV-1 infected patients with CD4 < 200 since 2002. This program may increase usage of ARV therapy and the emergence of HIV-1 drug resistance. Objectives To monitor HIV-1 ARV drug resistant codon mutation in Thailand before and after the “NAPHA” program. Materials and methods EDTA blood samples were collected from 542 HIV-1 infected subjects, who received ARV therapy in 1999 and 2001–2003, and perinatal chemoprophylaxis in 1998 and 2000. HIV-1 pol nucleotide sequences were analyzed. Results The percentage of drug resistant detection from the ARV therapy group in 1999 and 2001–2003 were 12.14 (34/280), 10.23 (9/88), 86.96 (20/23) and 57.55 (61/106), respectively. Of 332 NRTI drug resistant codon mutation, 226 (68.07%) were thymidine analogue mutations (TAMs). The percentage of TAMs detection in 1999 and 2001–2003 were 7.14 (20/280), 9.09 (8/88), 56.52 (13/23) and 43.34 (46/106), respectively. Of 105 NNRTI drug resistant codon mutation, 95 (90.48%) were related to nevirapine drug resistance. Conclusion Thailand may need more appropriate monitoring of drug resistance in the free ARV therapy program to protect the future usage of drugs by minimizing the emergence of drug resistance.