Background: While there is increasing literature on the health effects of work–life interference, few studies have investigated the relationship between a direct measure of work–life interference and objective sickness absence measures. The aim of this study is to investigate whether work–life interference is a risk factor for subsequent long-term sickness absence (LTSA). Methods: Data were derived from the Swedish Longitudinal Occupational Survey of Health 2010, 2012, 2014 and 2016. Data were linked to register data on LTSA (having at least one continuous period of medically certified sick leave exceeding 14 days) the following 2 years after each data collection wave. We applied generalized estimating equations, odds ratios (ORs) and 95% confidence intervals (CIs). The sample included 15 244 individuals (43.1% men and 56.9% women). Nearly a fifth of the sample (18.7%, n = 1110) started at least one period of LTSA at any point between 2010 and 2018. Results: Work–life interference was found to be a risk factor for subsequent LTSA (OR = 1.55; 95% CI = 1.44–1.67) even when adjusting for relevant factors including general health (OR = 1.39; 95% CI = 1.29–1.51). We found no significant moderating effect of gender. Conclusion: The results of this study indicate that work–life interference is a risk factor for subsequent LTSA for working men and women in Sweden.