Our aim in this study was to develop a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the measurement of atorvastatin, rosuvastatin and their major metabolites, and furthermore to evaluate patients’ adherence to statin therapy and to investigate the effect of statin therapy on various hematological and biochemical parameters. A simple protein precipitation was performed for the extraction of analytes and the extracted samples were injected directly. The levels of drugs and their metabolites were measured by the validated method in a total of 210 patients diagnosed with unstable angina pectoris (USAP), ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Various biochemical and hematological parameters were measured. The linearity ranges for atorvastatin and rosuvastatin were 1.22–2,500 and 0.97–2000 ng/ml, respectively. The inter-assay coefficient of variation for all analytes was ≤ 6%. In patients diagnosed with USAP, STEMI and NSTEMI, treatment compliance rates were 22.1, 23.5 and 41.2% for atorvastatin and 36.1, 40.2 and 67.1% for rosuvastatin, respectively. An economical, simple and reliable measurement method has been developed. Our findings support the poor patient compliance with statin therapy in the included population. It was observed that 6 months of statin treatment caused slight changes in biochemical and hematological parameters.