Background Tricyclic antidepressants (TCAs) are known to benefit subjects with functional nausea and vomiting (FNV), but it is not known if alternate neuromodulators are also beneficial. We retrospectively evaluated outcomes and clinical predictors of response in FNV subjects treated with any neuromodulator, including TCAs. Methods We identified 94 subjects (43.8±1.4 year, 79 F) with FNV (Rome III criteria) over a 12 year period, treated with neuromodulators and followed up for 8.5 ±1.1 months. Clinical presentation, demographics and gastric emptying study (GES) findings (when available) were extracted. Likert scales determined symptom severity at baseline and symptom response or remission at follow-up. Outcomes and predictors of response were evaluated using univariate and multivariate analyses. Results At least moderate symptom improvement was reported by 72.3%, and 22.3% had symptom remission. Proportions achieving moderate improvement and remission, and mean outcome Likert scores were similar regardless of neuromodulator agent used or GES status. On univariate and multivariate logistic regression analysis, baseline symptom severity affected symptom response, and pain negatively impacted symptom remission to treatment (p≤0.04 for each); GES status failed to predict treatment response or remission. Conclusions Symptom improvement with neuromodulators may be seen in over two-thirds of subjects with FNV regardless of the specific agent administered. Response may be suboptimal in pain predominant presentations.