spalipy performs detection-based astronomical image registration in Python. A source image is transformed to the pixel-coordinate system of a template image using their respective detections as tie-points by finding matching quads of detections. spalipy also includes an optional additional warping of the initial affine transformation via splines to achieve accurate registration in the case of non-homogeneous coordinate transforms. This is particularly useful in the case of optically distorted or wide field-of-view images.