For decades, two fusion modes were thought to control hormone and transmitter release essential to life: one facilitates release via fusion pore dilation and flattening (full-collapse), the other limits release by closing a narrow fusion pore (kiss-and-run). Using super-resolution STED microscopy to visualize fusion modes of dense-core vesicles in neuroendocrine cells, we found that facilitation of release was not mediated by full-collapse, but shrink-fusion, in which the Ω-profile generated by vesicle fusion shrank, but maintained a large non-dilating pore. We discovered that cells’ physiological osmotic pressure squeezed, but not dilated the Ω-profile, explaining why shrink-fusion prevailed over full-collapse. Instead of kiss-and-run, enlarge-fusion, in which Ω-profiles grew while maintaining a narrow pore, slowed down release. Shrink- and enlarge-fusion may thus be the yin and yang of fusion modes that contribute to account for diverse hormone and transmitter release kinetics observed in secretory cells, previously interpreted within the full-collapse/kiss-and-run framework.