Objectives: Cigarette smoking is a major cause of global morbidity and premature mortality. There is evidence that exposure to environmental tobacco smoke (ETS; "second-hand smoking" or "passive smoking") contributes substantially to ill health. However, it is difficult to establish causality given well-described problems of confounding and selection bias. We applied Mendelian randomisation (MR) to investigate the causal effects of ETS exposure. Design: We employed six MR estimation approaches: the effects of each parent's smoking on their offspring, the effects of each parent's smoking on the other parent, and the effects of self-reported exposure to second-hand smoking both inside and outside of the home. Setting: Genome-wide association studies (GWASs) with sample sizes ranging from 397,732 to 909,629 individuals of predominantly European ancestry. Interventions: To mimic exposure to ETS in the first four approaches, we used an individual's exposure to their relative's genetic liability to smoke, conditional on the original individual's genetic liability to smoke. In the final two approaches we used instruments associated with self-reported exposure to ETS. Outcomes: Lung cancer, chronic obstructive pulmonary disease (COPD), stroke, cardiovascular disease, hypertension, and depression. Results: Our findings support a causal effect of genetically predicted ETS exposure on lung cancer and COPD (odds per hour exposed in a typical week = 1.41 [95% CI: 1.23 to 1.61] and 1.11 [95% CI: 1.07 to 1.16] respectively). We did not find evidence supporting an effect on other outcomes. Discussion: ETS may cause both lung cancer and COPD. Although our results do not support an effect of ETS on other outcomes, this might reflect low statistical power to detect smaller effect sizes. These results support public health measures to limit exposure to ETS.