Context HIV infection has become a manageable chronic disease. There are few studies of pain and symptoms in the current treatment era. Objectives The primary objective was to determine the prevalence of and risk factors for pain and physical and psychological symptoms in a population of ambulatory HIV patients. Methods We performed a cross-sectional study using the Brief Pain Inventory and the Memorial Symptom Assessment Scale. Results We evaluated 156 individuals with a median age of 47.5 years (range 21–71), median time since HIV diagnosis of 11 years (range 3(interquartile range [IQR] 308–683). The majority (125, 80.6%) had an undetectable viral load. Seventy-six (48.7%) reported pain, of whom 39 (51.3%) had moderate to severe pain, and 43 (57.3%) had pain that caused moderate to severe interference with their lives. The median number of symptoms was eight (IQR 5–14.5) of 32 queried. In multivariable analyses, patients with psychiatric illness were 39.8% more likely to have pain (P Conclusion Pain and other physical and psychological symptoms were common among ambulatory HIV patients. Pain and symptoms were strongly associated with psychiatric illness and IV drug use. Future investigation should evaluate interventions that include psychiatric and substance abuse components for HIV patients with pain.