A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria: age, Mini Mental State Examination (MMSE) Global Deterioration Scale and Geriatric Depression Scale (GDS). After the initial screening and enrollment, the trial was run for 150 days in four phases: phase T0 (placebo treatment for 30 days), phases T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30 days of placebo treatment). Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances, or emotional-affective and relational behaviour. The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy. The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment (p < 0.0004); the same trend was observed in the scores for instability and negative feeling. No significant adverse drug reaction occurred during the trial. In conclusion, the statistical analysis of the data from this single-blind, multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment. Other reports indicate that this drug may be effective in the treatment of dementia.