Increased occurrence of sexual dysfunction (SD) among patients treated with highly active antiretroviral therapy (HAART) has been reported. To assess prevalence of self-reported SD and to identify factors related to this alteration with special focus to its relationship with adherence behavior, we conducted an intercohort analysis among HIV-infected persons treated with HAART. In an anonymous questionnaire investigating HAART nonadherence, patients were asked to report the occurrence of dysfunction in sexual activity over the previous 4 weeks. Among 612 participants, 125 (21%) reported some degree of SD. "Moderate"/"severe" alterations were reported in 6% and were independently associated with self-reported worsening of viro-immunological parameters (OR 3.90; 95% CI 1.08-14.18), higher symptom score (OR 1.13; 95% CI 1.05-1.22), and reporting abnormal fat accumulation (OR 4.33; 95% CI 1.55-12.11). Furthermore, nonadherent persons had an increased risk of SD (OR 3.44; 95% CI 1.30-9.08). In conclusion, patients' perceived SD represents a relevant problem for HIV-infected persons treated with antiretrovirals and is strongly associated with suboptimal HAART adherence.