SUMMARY Seismically triggered subaqueous mass movements in lakes may generate tsunamis that can cause significant damage on the shore. In this study, we assess the seismic response and stability of subaqueous slopes in Swiss lakes based on recorded seismological data, historical and geological information and geotechnical surveys. We performed seismic investigations at multiple locations in Lake Lucerne using Ocean Bottom Seismometers (OBS). For these locations, we derived ground-motion amplification functions from local and regional earthquakes and horizontal-to-vertical spectral ratios (H/V) from the earthquake and ambient vibration recordings. The results show (1) very high amplification levels, often exceeding values of 50–100 in the frequency range between 1 and 10 Hz, (2) the fundamental frequency of resonance in the range of 0.5–3.5 Hz and (3) laterally variable site response even for closely located stations. We sought also the signatures of non-linear site response in the H/V curves or ground-motion amplification functions but found only weak indicative effects and no clear evidence. This is most likely due to the low levels of ground motion recorded during the OBS campaigns. We conducted back analyses of historical earthquakes in Switzerland with available documental and/or geological evidence of induced (tsunamigenic) subaqueous slope failures in Swiss lakes. The data set of historical events was complemented with a selection of instrumentally recorded earthquakes in Switzerland. For the analyses, we selected multiple sites in Swiss lakes which failed in the past or are prone to failure in the future. We modelled the ground motion at these locations assuming Swiss standard reference rock conditions (vs30 = 1105 m s−1). The modelled ground motion intensity measures (IM) included peak ground acceleration (PGA), peak ground velocity (PGV) and pseudospectral acceleration (PSA) at 0.3, 1 and 2 s. We estimated the minimum ground motion and macroseismic intensity at reference rock conditions required to trigger the failures of subaqueous slopes. In addition, we defined a threshold for the seismic triggering of such failures in terms of moment magnitude (Mw) and epicentral distance (Re) as: $$\begin{eqnarray} M_{\rm w}=2.891+1.904\log_{10}(R_e+5.166)\: {\rm for}\: R_e\ge 3.7\: {\rm km}. \end{eqnarray}$$ Our results are consistent with previous studies based on worldwide observations. Furthermore, we related the modelled ground motions to the Swiss seismic hazard products and estimated the return period of critical ground shaking responsible for triggering subaqueous slope failures (with potential for tsunami generation) to be in the range of 36–224 yr. Finally, based on previously collected geotechnical data (in situ Cone Penetration Testing and laboratory sediment analysis), we determined the most likely values of the seismic coefficient k to be used with the ground motion IMs modelled at reference rock conditions in infinite slope stability analyses to estimate the factor of safety (FS). For PGA, we found a k = 1; for PGV, k = 2; for PSA0.3s, k = 0.6; for PSA1s, k = 2 and for PSA2s, k = 5.5. These estimates are conservative and affected by the trade-off between the thickness of unconsolidated sediments and the slope angle. Thus, we recommend applying them to slopes with a low-to-moderate gradient (<15°) and sediment thickness of more than 2 m.