Introduction: The aim of the study was to examine the effect of oral administration of L-arginine on the quadriceps strength in smokers and non-smokers, as well as on the quadriceps strength in smokers with regard to the age at smoking onset and the number of cigarettes smoked. Subjects and methods: The study included 164 subjects, 81 (49.4%) of whom were smokers, while the rest were non-smokers. All the patients were measured for body weight, height, BMI (Body Mass Index), waist circumference, heart rate, saturation (SpO2), blood pressure, respiratory index, and thoracic spine mobility index. Spirometry was performed and patients with FEV1 / FVC < 0.70 were excluded. The patients' fitness status, cardiorespiratory, and muscular ability were tested using a 6-minute walk test and a bicycle ergometer ride. The values of maximum oxygen uptake (VO2 max) and pulse were measured. Each respondent assessed the intensity of dyspnea on Borg's dyspnea scale before and after a 6-minute walk test and a bicycle ergometer. The quadriceps strength test was performed on the Biodex isokinetic device on one occasion without L-arginine and on the other occasion 90 minutes after the oral administration of L-arginine. All patients completed the CAT questionnaire (COPD Assessment Test), the DASS-21 questionnaire (Depression Anxiety Stress Scale - 21), and the IPAQ questionnaire (International Physical Activity Questionnaire). For smokers, the age at smoking onset and pack-years (number of cigarettes smoked per day / 20 x the number of years of smoking experience) were recorded. Results: A strong negative correlation was observed between the age at smoking onset and the change in quadriceps strength (Spearman's coefficient r = –0.602). Arginine therapy had a greater effect on those who started smoking at an earlier age. According to the results of Spearman's correlation test, the average number of cigarettes smoked was statistically significantly associated with changes in quadriceps strength after arginine therapy (r = 0.248; p = 0.031), with CAT test values (r = 0.242; p = 0.029). The age at smoking onset was statistically significantly associated with the changes in quadriceps strength after arginine therapy (Spearman's correlation test; p < 0.001). Conclusion: The results of the study confirmed an increase in quadriceps strength measured on an isokinetic device after oral administration of L-arginine in smokers and non-smokers and that this increase was more pronounced in smokers who started smoking at an earlier age and smoked more cigarettes per day.