Irrational and excessive use of antibiotics increases resistance to these preparations. Antimicrobial resistance is a serious public health problem worldwide. The main goal of our study was to evaluate the use of antibiotics (indications, dosage, and treatment duration) in daily family doctors' practice and nonadherence to guidelines on rational antibiotic therapy. A retrospective study of records regarding the prescription of antibiotics for patients in two outpatient settings during the period of January 1, 2005, to December 31, 2005 was performed in Clinic of Family Medicine at Kaunas University of Medicine. Rationality of antibiotic therapy was evaluated according for adherence to published guidelines. A descriptive and comparative statistical analysis of data was processed with SPSS 13.0 program. There were 2935 patients in both outpatient settings (1285 and 1650, respectively). During the period of January 1, 2005, to December 31, 2005, antibiotics were prescribed in 210 cases for various reasons (71 (33.8%) and 139 (66.2%), respectively). A total of 184 (6.3%) patients received antibiotic therapy. It was determined that only in 9.5% of all cases, antibiotics were administered in keeping with the recommendations for rational antibiotic therapy. Only two treatment cases (1%) were based on bacteriological analysis. According to indications, appropriate antibiotics were prescribed in 42.9% of cases. The dosage of antibiotics was adjusted properly in 56.2% of cases, and even in 82.9% of cases, the duration of antibiotic therapy fulfilled the guidelines on rational antibiotic use. More rational antibiotic therapy was practiced in the second outpatient setting (10.8%) compared to the first outpatient setting (7%) (p<0.05). The most irrationally antibiotics were prescribed for the treatment of urinary tract and ocular infections.