The objective of this study was to prospectively evaluate the impact of diabetes on HRQOL at baseline and 6-months following ACS treated by PCI and to determine which predictors: demographic, clinical, and other variables influence QOL results in physical component summary (PCS) and mental component summary (MCS) of SF-36 health survey. The 120 consecutive patients (mean age 62.5, SD ± 9.8) with acute coronary syndrome ACS including non-ST-elevation myocardial infarction NSTEMI, n = 60 and ST-elevation myocardial infarction STEMI, n = 60 were entered into the study. Each patient was prospectively interviewed at baseline (at discharge) and 6-months following ACS. We relied on previously validated questionnaire to assess the patient's overall health perception, namely the SF-36 health survey. Generally, the whole group demonstrated the better PCS score at 6-month follow-up: 54.7 versus 55.5; P < 0.0001. With regard to PCS, an increase in life quality results was observed in both groups. However, it should be emphasize that the diabetic group demonstrated considerably lower life quality baseline. Also, the whole group demonstrated better MCS score at 6-month follow-up: 55.9 versus 56.5; P < 0.0001. The influence of diabetes, multivessel disease, hypertension, and the high triglyceride level have negative impact on life quality evaluation, whereas male patients and patients with ACS-STEMI had better quality of life results. The influence of diabetes, multivessel disease, hypertension, and the high triglyceride level have negative impact on life quality evaluation, whereas male patients and patients with ACS-STEMI had better quality of life results. The influence of diabetes, the history of myocardial infarction, and the high triglyceride level have negative impact on life quality evaluation. Patients with ACS-STEMI had better quality of life results. The influence of diabetes, the history of myocardial infarction, and the high triglyceride level have negative impact on quality of life evaluation. Male patients had better quality of life results. (1) Diabetic patients obtain worse life quality results than non-diabetic patients, both at baseline and 6-months following PCI. (2) Positive predictors of patient's life quality are the male sex and clinical manifestation of the disease (STEMI). (3) As regards PCS, negative predictors of patient's life quality are diabetes, multivessel disease, high triglyceride level, and arterial hypertension. (4) As regards MCS, negative predictors are diabetes, the history of myocardial infarction, and high triglyceride level.