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This study examined the relationship of weather conditions, together with sex and country of origin, with running performance in the Boston Marathon from 1972 to 2018. A total of 580,990 observations from 382,209 different finishers were analyzed using Generalized Additive Mixed Models. Different groups and subgroups were considered such as all runners, near elite 101:200 finishers, near elite 21:100, annual top ten finishers and annual winners. Weather conditions, over the hours of the event, were average air temperature (°C), total precipitations (mm), wet-bulb globe temperature (WBGT) (°C), wind speed (km/h), wind direction (head wind, side wind, tail wind) and barometric pressure (hPa). These effects were examined in a multi-variable model, together with: sex, country of origin, calendar year, an interaction term country:sex and a spline smooth term in function of calendar year and sex. The average temperature, when increasing by 1°C, was related to worsened performance (by 00:01:47 h:min:sec for all finishers and by 00:00:20 h:min:sec for annual winners). Also, the pressure and wet-bulb globe temperature, when increasing, were related to worsened performances. Tail wind improved performances of all groups. Increasing precipitation was significantly (p<0.05) related to worsened performances in all groups except annual winners. Increasing wind speed was also related to worsened performances in all finishers and near elite groups. Kenyans and Ethiopians were the fastest nationalities. The sex differences (men faster than women in all groups) were the largest in near elite groups. Our findings contributed to the knowledge of the performance in Boston Marathon across calendar years, considering as main effects weather conditions, country of origin and sex. [ABSTRACT FROM AUTHOR]