Many studies analyze the effects of many drugs on quality of life (QOL). The aim of this study is to compare the effectiveness of the leukotriene receptor antagonists on QOL. Forty mild asthmatic patients were randomized for 12 treatment-weeks and divided into two groups: the first group was treated with montelukast (MON; 10 mg daily) and the second one was treated with zafirlukast (ZAF; 40 mg daily). All patients underwent clinical examination, spirometry, and completed the Asthma Quality of Life Questionnaire. For each domain, a value of 1 (maximal impairment) and 7 (no impairment) was used. The MON group had in all items a basal median value of 4.7 compared with 5.5 after the treatment (p < 0.05). For physical activities, the mean value was 5.1 compared with 5.9 (p < 0.05). The median scores of 12 symptoms and 5 emotion items were 5.0 and 4.7, significantly lower than 5.7 and 5.3 (p < 0.05). For the environmental stimuli domain, the mean value was 4.6 compared with 5.3 (p < 0.05). The ZAF group had in all items a basal median value of 4.8 compared with 5.7 after the treatment (p < 0.05). For physical activities, the value was 5.0 compared with 5.7 (p < 0.05). Median scores of 12 symptoms and 5 emotions were 4.9 and 4.8, significantly lower than 5.6 and 5.8 (p < 0.05). For the environmental stimuli domain, the median score was 4.7, significantly lower than 5.6 (p < 0.05). The results did not show many differences between the two treatments, showing significant improvement for both MON and ZAF on QOL.