Purpose: College students with chronic illnesses are vulnerable to poor adjustment, but it remains unclear how these students differ from healthy peers. This study compares psychosocial adjustment and risky behavior between students with and without chronic illnesses. Participants: Participants (N = 629, 78% Caucasian, 77% Female) were recruited from universities. Methods: Participants completed measures of illness history, anxiety, depression, stressful life events, social support, and risky behavior. Results: College students with chronic illnesses demonstrated significantly greater symptoms of anxiety F(1,620) = 8.742, p < 0.003, depression F(1,614) = 26.947, p < 0.001, more stressful life events F(1,476) = 23.671, p < 0.001, and lower social support F(1,613) = 15.645, p < 0.001. No differences in risky behaviors between groups emerged F(1,601) = 3.432, p = 0.064. An indirect effect of health status on risk-taking behavior was observed [b = 0.677, 95% CI (0.351, 1.072)] partially mediated by depression. Conclusion: College students with chronic illnesses demonstrated worse psychosocial outcomes than healthy students, warranting programs to support these students. Depressive symptoms partially mediated risky behavior.