The aim of this study was to expand our knowledge on the association between various environmental, psychological and heritable factors and the perception of acute experimentally induced mechanical pain. This cross-sectional study included 2,500 adults of both sexes older than 18 years, living on the island of Vis, Korčula and the city of Split. Using an algometer, we caused pressure on the index finger of the right and left hand of the subject, which at a certain pressure turned into a painful stimulus. We measured the pain threshold and pain tolerance, and from the difference between the tolerance and pain threshold, we calculated the pain interval as a measure that indicates the subject's ability to tolerate the pain. In order to collect data on socio-demographic, psychological, health and behavioral determinants, an extensive questionnaire was used. In the data analysis, we calculated the heritability of the pain threshold, tolerance and pain interval for subjects from the islands of Vis and Korčula. The association between various environmental and psychological determinants and pain perception was analyzed using bivariate statistical methods, as well as multivariate linear regression analysis. The variables included in the regression analysis as determinants of experimental acute pain were age, sex, place of residence, number of years of education, material status, waist-to-hip ratio, presence of chronic diseases, smoking, alcohol consumption, physical activity, mental distress, psychoticism, extroversion, neuroticism, tendency to lie and optimism. The heritability of pain threshold in subjects from the island of Vis was 50.8% on the right and 36.2% on the left hand, while the heritability of pain tolerance was 54.2% on the right hand, but it was not statistically significant on the left hand. The heritability of pain threshold in subjects from the island of Korčula was 53.0% on the right and 49.8% on the left hand, the heritability of pain tolerance was 50.3% on the right and 53.8% on the left hand, while the heritability of pain interval was 45.4% on the right hand and 47.3% on the left hand. Dispositional optimism was significantly and positively associated with pain tolerance induced by mechanical pressure on the right hand (β=0.46; p=0.030) and on the left hand (β=0.55; p=0.015). Also, pain interval was positively associated to dispositional optimism on both the right hand (β=0.42; p=0.030), and the left hand (β=0.46; p=0.029). On the other hand, there was no statistically significant association between pain threshold and dispositional optimism. This suggests that more optimistic subjects were able to tolerate pain more successfully, despite being just as sensitive to pain as less optimistic subjects. Given that we measured pain perception on both hands, we had the opportunity to investigate how the perception of pain is affected by the dominance of the subject's hand. The results indicate that there were no differences in the perception of pain between right-handed, 154 left-handed and ambidextrous people, but there were certain differences within each of the groups. For instance, right-handed people had a higher pain threshold, pain tolerance, and pain interval on the dominant (right) hand, while these findings have not been confirmed in lefthanded people. This study shows that the perception of pain is influenced by a large number of different factors and characteristics that together create the individual experience of pain. Among these factors, optimism stands out as a factor that could be used for creating psychological interventions in the future, with the aim of increasing optimism and thus enabling easier coping with painful stimuli and more successful pain tolerance.