Cigarette smoking has been shown to delay soft tissue healing and complicate musculoskeletal recovery. Its deleterious effects have been proven in bone and soft tissue, although to a much more limited fashion in ligament or tendon. We exposed 120 experimental mice to two cigarettes per day for 2 months and then induced a blunt medial collateral ligament (MCL) injury. Mice were assigned to three groups: the first group exposed to two cigarettes per day after injury, the second group exposed to one cigarette per day after injury, and the third group not exposed after injury. A fourth, no-smoking group served as control. The cut and contralateral intact ligaments were biomechanically tested to failure at 7 and 28 days. The ligaments of mice exposed to cigarette smoke were weaker (p = 0.02) and less stiff (p = 0.0004) at 28 days (3.2 N, 3.5 N/mm) compared with those of mice exposed to cigarette smoke for 7 days (3.9 N, 4.7 N/mm). The ligaments of mice exposed to cigarette smoke were weaker (p = 0.02) and less stiff (p = 0.01) at 28 days compared with control mice at 28 days. Between 7 and 28 days, smoking had a deleterious effect on healing manifested as weaker and less stiff ligaments. However, our findings did not support a dose-dependent effect of cigarette exposure on the tensile mechanical properties of ligaments.