The objective of this study was to examine the associations of working conditions with major weight gain. Three different groups of work-related factors were examined: (i) work arrangements, (ii) physical working conditions, and (iii) psychosocial working conditions. The data are based on the Helsinki Health Study (HHS) questionnaire surveys. A baseline mail survey was made among middle-aged employees of the City of Helsinki in 2000-2002. A follow-up survey was made in 2007. Regression analyses with odds ratios and 95% confidence intervals were calculated. During the 5- to 7-year follow-up, 26% of women and 24% of men gained in weight 5 kg or more. Working conditions were mostly unassociated with weight gain. However, nighttime shift work, physical threat at work, and hazardous exposures at work were moderately associated with weight gain. More attention should be devoted to the prevention of weight gain in general and among risk groups in particular.