Purpose: Because the transmission of HIV and hepatitis C virus (HCV)is associated with high risk behaviors, we investigated risk attitudes and their determinants in patients with HIV, HCV, and HIV/HCV co-infection. We also compared risk attitudes of patients with those of primary care house officers. Methods: We assessed risk attitudes of 203 patients with HIV, HCV, or both from Cincinnati and Pittsburgh and of 81 primary care house officers from Cincinnati by using the modified 6-item Jackson Personality Inventory (JPI; range: 6 [most risk-averse] – 36 [most risk-seeking]). For the patients, we used linear regression methods to analyze JPI scores by disease type, SF-12 Mental Component Summary score (MCS; range, 0-100), Duke Religion Index score (range: 1 [low] – 5 [high], on each of 3 subsets), and other clinical, demographic, and psychosocial factors. Results: Of the 203 patients, 59 (29%) had HIV, 69 (34%) had HCV, and 75 (37%) had co-infection. Their mean (SD) age was 45.6 (8.3) years; 45 (22%) were women, 118 (58%) were white, 124 (61%) were single, 82 (42%) had a history of injection drug use, 153 (75%) had health insurance, and 166 (82%) belonged to some religion. For the house officers, the mean (SD) age was 28.7 (3.1) years; 41 (51%) were women and 54 (68%) were white. The mean (SD) JPI score for house officers, 20.2 (4.5), exceeded that of patients, 18.9 (5.6), indicating that house officers were more risk-seeking than patients (p=0.046). Among patients, the mean (SD) JPI scores were 19.5 (5.1) for patients with HIV mono-infection, 20.0 (6.2) for patients with HCV mono-infection, and 17.4 (5.3) for the co-infected group, indicating that co-infected patients were the least risk-seeking (p=0.0028). In multivariable models, greater risk-seeking attitudes correlated with mono-infection, less frequent participation in religions services, better MCS mental health scores, male sex, and having health insurance (R²=0.18). Conclusion: Surprisingly, patients with HIV, HCV, or both are slightly less risk-seeking than primary care house officers. Among patients, co-infected patients are the least risk-seeking, although some of the differences are accounted for by differences in personal characteristics.