Health-related quality of life (HRQoL) has become increasingly important as the measure of treatment outcomes. Studies on HRQoL after an open heart surgery in Thailand are limited. The aim of this study was to evaluate the HRQoL improvements in terms of physical activity, physical and mental health, depression, cognitive function, chest pain after coronary artery bypass graft (CABG) and overall HRQoL at 3 and 5 months after the discharge from hospitalization for the heart surgery. Total of 122 adult patients were interviewed using a set of questionnaires before the operation, 3 months and 5 months thereafter. Several HRQoL measures including Duke Activity Status Index (DASI) [12 items], 9-THAI (Thai Health status Assessment Instrument) [8 items], Centers for Epidemiological Studies-Depression Scale (CES-D) [20 items], RAND cognitive function [6 items], Seattle Angina Questionnaire (SAQ) [4 items], and EuroQoL Visual Analogue Scale (EQ5D VAS) were used. The study was conducted at a tertiary care center of heart surgery in the northeastern region of Thailand, and data were collected during June 2006 to April 2007. The mean age of patients was 50.3 ± 13.6 years. HRQoL improvements after the surgery were reported as follows. The DASI scores increased by 8.6 ± 14.6 and 11.2 ± 14.4 at 3 and 5 months, respectively (p < 0.001). The 9-THAI physical score increased by 3.6 ± 22.4 (p = 0.1) and 10.1 ± 19.9 (p <0.001) at 3 and 5 months. The 9-THAI mental score increased by 0.3 ± 22.9 (p = 0.9) and 4.9 ± 19.6 (p < 0.01) at 3 and 5 months. The CES-D score decreased by 2.3 ± 7.9 (p < 0.01) and 2.7 ± 7.6 (p < 0.001) at 3 and 5 months. The RAND cognitive function score increased by 3.6 ± 16.4 (p < 0.05) and 6.0 ± 16.2 (p < 0.01) at 3 and 5 months. The angina frequency score increased by 50.0 ± 30.7 and 52.5 ± 28.0 at 3 and 5 months (p < 0.001). The angina stability score increased by 43.7 ± 34.4 and 42.5 ± 35.7 at 3 and 5 months (p < 0.001). The treatment satisfaction score increased by 6.6 ± 3.2 (p = 0.05) and 5.6 ± 20.8 (p = 0.1) at 3 and 5 months. The overall HRQoL measure, EQ5D-based utility score increased by 8.6 ± 25.2 and 12.0 ± 24.2 at 3 and 5 months (p < 0.001). Patients who were undergone the success open heart surgery had the significant improvement in terms of physical health, mental health, cognitive function, clinical conditions, and overall HRQoL at 3- and 5-month follow-up after the surgery.