Let [Formula: see text] be a complete, model complete o-minimal theory extending the theory [Formula: see text] of real closed ordered fields in some appropriate language [Formula: see text]. We study derivations [Formula: see text] on models [Formula: see text]. We introduce the notion of a [Formula: see text]-derivation: a derivation which is compatible with the [Formula: see text]-definable [Formula: see text]-functions on [Formula: see text]. We show that the theory of [Formula: see text]-models with a [Formula: see text]-derivation has a model completion [Formula: see text]. The derivation in models [Formula: see text] behaves “generically”, it is wildly discontinuous and its kernel is a dense elementary [Formula: see text]-substructure of [Formula: see text]. If [Formula: see text], then [Formula: see text] is the theory of closed ordered differential fields (CODFs) as introduced by Michael Singer. We are able to recover many of the known facts about CODF in our setting. Among other things, we show that [Formula: see text] has [Formula: see text] as its open core, that [Formula: see text] is distal, and that [Formula: see text] eliminates imaginaries. We also show that the theory of [Formula: see text]-models with finitely many commuting [Formula: see text]-derivations has a model completion.