In lib-pypy/_sqlite3.py, line 239 (in Win 1.5 stable release) in class Connection(object): def __init__(self, database, isolation_level="", detect_types=0, timeout=None, cached_statements=None, factory=None): ...might need to become: def __init__(self, database, isolation_level="", detect_types=0, timeout=None, cached_statements=None, factory=None, *check_same_thread=False *): I am testing the web framework web2py against pypy, and this issue came up. I don't know too much about sqlite itself. Spent a lot of time modifying code to explicitly close file handles because of the different behaviour of the ref counting cpython vs. the gc pypy.