Interstitial lung disease (ILD) is common in patients with myositis and is related with the presence of antisynthetase autoantibodies (aSA). Together with other manifestations, the resulting condition is known as the antisynthetase syndrome (ASS). Contact with certain environmental and occupational agents is also associated with the development of ILD. The objective of this study was to analyze occupational exposure and associated clinical manifestations in a cohort of patients with ASS. aSA had been identified by line immunoassay and confirmed by immunoprecipitation. Serial pulmonary function tests had been carried out to assess lung function. Thirty-two ASS patients and a control group of 32 myositis patients without aSA underwent a specific questionnaire interview to evaluate their cumulative exposure to biological dust, mineral dust, and gases/fumes up to disease onset. Comparisons were done with the Fisher exact test and Mann-Whitney test. Out from 32 ASS patients (median age, 42.7 yeras; IQR 32.2-52.5), twenty-six patients had anti-Jo-1, three anti-PL-12, and three anti-PL-7. Nine had polymyositis, 15 dermatomyositis, one amyopathic dermatomyositis, and seven pure ILD without myositis. Sixteen ASS patients (50 %) and seven (22 %) myositis patients without aSA had ever been highly exposed to dust, gases, or fumes (p < 0.05). A more than 10 % improvement in forced vital capacity occurred in 61 % of highly exposed patients and 23 % of those with low/no exposure (p = 0.06) over the observation period. In conclusion, a high percentage of patients with ASS had been exposed to dusts, gases, or fumes.