Psoriasis is a chronic inflammatory disease associated with significant impairment in quality of life. Although quality of life in patients with psoriasis has been widely studied, there is little evidence regarding the impact of psoriasis on major life-changing decisions (MLCD). The aims of this study are to describe the impact of psoriasis on MLCD and to explore the potential clinical factors associated with MLCD. This cross-sectional study included 113 patients with psoriasis, regardless of disease severity, duration, or current treatment. The impact of the disease on different MLCD, including those related to professional career, decision of having children, choice of clothing, and leisure activities, was explored using Likert scales. Mean age was 51 years old and female to male ratio was 1.08 (54/50). The mean Psoriasis Area Severity Index was 3.75, and 30% (35/113) of the patients had psoriatic arthropathy. The most affected MLCD were career choice (median (interquartile range) score 3 (2-4)), social relationships (2 (1-3)), choice of clothing (2 (1-3)), job performance, absenteeism, and choice of holiday destination (1 (0-2)). Female sex, early age of onset and psoriatic arthropathy were associated with a greater impact of the disease on MLCD (p < 0.05). The results showed that a range of MLCD are affected in patients with psoriasis, such as career choice, job performance, absenteeism, or choice of clothing. Female sex, psoriatic arthritis and early age of onset are factors associated with a greater impact on MLCD. In order to limit the long-term negative effects of psoriasis on patients, special attention should be paid to detection of psoriatic arthritis, and to patients with early disease onset.