Background The Mood Disorder Questionnaire (MDQ) was designed as a screening questionnaire for bipolar disorder. Previous research has raised questions about the suitability of the MDQ structure for screening for bipolar II disorder. This study investigated the optimal sensitivity and specificity cut-off thresholds for the MDQ in bipolar I and bipolar II patients in a UK sample. Methods The MDQ was administered to patients before attending a tertiary mood disorders clinic. Diagnostic interviews were used to determine DSM-IV diagnoses and these were used as the gold standard against which to investigate the performance of the MDQ. Results 54 patients with bipolar spectrum disorder and 73 patients with unipolar depressive disorder completed the MDQ. With the original scoring criteria (symptoms and supplementary questions) the sensitivity for bipolar disorder was 0.76 (bipolar I disorder 0.83, bipolar II disorder 0.67) with specificity 0.86. The optimal cut-off score in the current sample was a score of 9 or more endorsed symptoms without applying the supplementary questions (sensitivity of 0.90 and 0.88 for bipolar I and bipolar II groups respectively with a specificity of 0.90). Limitations The sample was drawn from a tertiary mood disorders clinic. Conclusions The MDQ appears to be a useful screening tool for bipolar spectrum disorder in UK psychiatric practice with sensitivity for bipolar II disorder improved by dropping the supplementary sections. Further investigation of the optimal cut-off scores of the MDQ is needed to determine its utility in non-specialist and community based samples.