To assess the influence of an oral contraceptive (OC) containing 20 microg ethinylestradiol and 150 microg desogestrel on quality of life and subjective symptoms. In this multicenter observational evaluation performed in Germany, 3679 first-time OC users were included. They were treated by 623 physicians. The women completed quality of life questionnaires (Q-LES-Q) at baseline and after three treatment cycles. The mean age of users (+/- SD) was 22.5 +/- 7.1 years, with 47% of the women aged between 15 and 20 years. Half of the women reported skin problems at inclusion and, of these, 36% reported disappearance of the problems after three treatment cycles. Most women suffering from subjective symptoms (headache, nausea, nervousness, breast tenderness and depressive moods) at baseline reported improvements (57-71%) in their symptoms after using the OC for three cycles. Adverse events were reported by 4% of users; the most frequently reported were bleeding irregularities (1.7%). The total quality-of-life score and all its 13 individual items improved significantly (p < 0.0001), with the largest improvements in sex life and mood. Almost all (94%) women were either very satisfied or satisfied with the medication. The OC containing ethinylestradiol and desogestrel significantly improved the quality of life and subjective symptoms. The OC was well tolerated by first-time users.