Men who have sex with men (MSM) have an increased risk of contracting sexually transmitted diseases (STDs) and HIV. Studies of their health-related quality of life (HRQL) are uncommon, though such studies may provide additional knowledge that is of interest in counselling and care. The HRQL in MSM attending a clinic for STD- and HIV testing in Stockholm, Sweden, was investigated in 1996 and 2004, measured by means of the Swedish Health-Related Quality of Life questionnaire. The results were compared with those for men from a general Swedish population sample and with HIV-infected men. The HIV-negative MSM had significantly worse emotional wellbeing, satisfaction with family life, relation to their partner and general health perception, and better physical HRQL compared with the general Swedish population. There were no differences in the emotional and family dimensions between HIV-infected and HIV-negative MSM, but the HIV-negative group scored at a higher level in respect of their physical and general health than the HIV-infected group. No apparent differences over time were seen in the HIV-negative group. This study shows that psychosocial HRQL is lower for MSM than for a general male population sample, which calls for increased attention in the care of MSM patients.