We conducted a study on 367 patients (86% female, 14% male; mean age 37±15 years) suffering from migraine with and without aura and chronic tension–type headache to evaluate the incidence of weight gain, an undesirable side effect observed during prophylactic therapy in primary headaches. Patients treated with amitriptyline (20 and 40 mg), pizotifen (1 mg), propranolol (80–160 mg), atenolol (50–100 mg), verapamil (160–240 mg), valproate (600 mg) and gabapentin (900–1200 mg) were evaluated after a period of 3 and 6 months. In particular, 89 patients were assessed (78% female, 22% male) at 6 months, of whom 10 were in treatment with amitriptyline 20 mg, 19 with amitriptyline 40 mg, 7 with pizotifen (1 mg), 13 with propranolol (80–160 mg), 4 with verapamil (160 mg), 10 with valproate (600 mg), 15 with atenolol (50 mg) and 11 with gabapentin (900–1200 mg). The control group consisted of 97 patients with migraine (79% female, 21% male; mean age 35±16 years) without indication for prophylactic therapy. Weight variations ≥1 kg were considered. After 6 months of therapy, the percentage of patients with weight gain was 86% with pizotifen (6/7; mean weight increase 4.4±2.5 kg), 60% with amitriptyline 20 mg (6/10; 3.1±1.6), 47% with amitriptyline 40 mg (9/19; 5.4±2.7), 25% with valproate 600 mg (2/8, 3.0±2.8 kg), 25% with verapamil (1/4, 2.5 kg), 20% with atenolol (3/15, 1.7±0.6 kg), 9% with gabapentin (1/11, 1.5 kg) and 8% with propranolol (1/13; 6 kg). We conclude that propranolol, gabapentin, atenolol, verapamil and valproate affect body weight in a modest percentage of patients at 6 months. A greater mean weight gain at 6 months was found in patients treated with pizotifen, amitriptyline, and, in one patient out of 13, with propranolol.