Objective: To examine the feasibility, efficacy, and safety of a structured 12-week exercise training program for a predominantly African-American group of adults with multiple health conditions who reside in difficult social environments. Methods: A total of 37 females and 7 males (mean age, 54.1 years) participated in an exercise training regimen 3 days per week for 60 minutes per day (cardiovascular, 30 minutes; strength, 20 minutes; and flexibility, 10 minutes). Outcome measures included peak VO2 (mL min -1, mL kg -1 min -1); upper and lower body strength (strength); hand-grip strength (GS); body weight (BW); total skin folds (TS); waist-to-hip ratio (WHR); hamstring/low-back flexibility (HLBF); and shoulder flexibility (SF). Results: Compared to the control group, the exercise group showed significant gains in peak VO2 (p < 0.01); strength (p < 0.01); and body composition (TS, p < 0.01). There was no significant difference between the exercise and control groups on BW, WHR, HLBF, and GS. Of a total 1116 exercise sessions (31 experimental participants x 36 sessions), 87% of the sessions were attended. Conclusion: A structured exercise-training program can provide substantial improvement in strength and cardiovascular fitness in low-income, sedentary adults with multiple chronic conditions and/or risk factors for chronic conditions. Future research should explore simple home-based and community-based physical activity interventions that provide ongoing support for increasing and maintaining physical activity participation in this cohort.